| 1 | Sacred 𓁞 Medicine | [strong current] Cellular Regeneration | Remove old codes & DNA reprog... | 3640 | 540 | 52 | 90.0 | positive | 13:44 | Welcome bright light. Prepare to receive a cellular regeneration. Our current main theme is divinely orchestrated. And I have been directed to your energetic field to offer a deep cellular cleanse and reprogramming. Our cells, apart from being such an important part of our physical body, they keep our organism alive and well. They also store loads of information from the light spectrum where traumas, motions and different levels of consciousness get stored. As all conditions are energetically rooted, these are monocresonances in cellular memory create manifestations of it in the physical. If this video found you and you are still here, you are being aligned to its content. And chances are that your system needs some help connecting back your cells to their divine blueprint in order to fully benefit of the universal and planetary energetic codes flowing as we speak. The best way to fully receive and allow is simply to do that. And trust. Please comment, share and subscribe if you haven't done it already. I love hearing from you and how I feel into this community that we are co-creating together. If you feel cold to rise to awaken your cub body, through the Egyptian lineage, and go deeper into the exploration of your food potential, join me for a small group of sacred Kundalini rice and ceremony. The links are below and I would love to see you there. The links are below and I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. I would love to see you there. As we are arriving to the end of the session, please deepen your breath so you allow this coach to settle in your body in the upgraded system. Can integrate smoothly. As usual, I would like to thank you all for your support and presence. I send you all so much love. See you in the next one. | ↗ |
| 2 | Modern Healthspan | Single Gene Reverses 13+ Years of Aging - Safer Than Yamanaka Factors | 11355 | 592 | 84 | 87.1 | positive | 6:05 | [Music] What if one gene was able to provide the same or better rejuvenation with epigenetic reprogramming than the Yamanaka factors and without the risk of cancer? A new preprint just released documents a gene sp0000 that turns back the clock of cells without the danger of pluropotency and the loss of cell identity that are inherent when using the ammonaka factors. This addresses one of the main concerns with reprogramming as a therapy and is a great step forward. Let's look at what they found and why it's so important. Epigenetics is the layer of control that exists on top of the DNA. It uses activities such as methylation to control which genes are turned on and which are turned off. The epigenetics of cells changes in a predictable way as we age, which is what the epigenetic clocks use as a basis to measure biological age. Changing the epigenetic profile of a cell so that it is younger has been shown to make the cell behave as a more youthful cell. This has been possible with the yamanaka factors. These are four genes 2, zox 2, kf4 and cmix abbreviated tokm which when expressed in a cell can turn it back into a pluropotent stem cell. So a pluropotent stem cell is a cell that can become any type of cell in the body like a master cell that hasn't decided what to become yet. On the way to becoming pluropotent, the cell also becomes younger leading to the process to be called partial reprogramming. The problem with this is that it can lead to loss of cell identity which is necessary for a cell to become puropotent. So for example, a skin cell no longer remembers that it's a skin cell and may become a liver cell instead. This means that the cell no longer functions correctly in its place and may become cancerous. When delivering Yamanaka factors in vivo, that is to living tissue, it's very difficult to control how much reprogramming each cell gets. And so to be sure no cell changes identity. This is a major roadblock for partial reprogramming with the Yamanaka factors. But what if we could separate the rejuvenation effect from the pluropotency problem? The original Yamanaka factors were chosen because of their ability to induce puropotent stem cells. Rejuvenation was almost a side effect. So the team at Shift Biosciences took a different approach. They built a high throughput screening system that could test thousands of genes simultaneously using a rejuvenation first strategy to measure success. They developed AC3, a precise aging clock that determines a cell's biological age by analyzing gene activity patterns. This allowed them to quickly identify genes that reversed aging without the dangerous side effects leading them to discover SP0000. Now, the name does have three zeros, but from now on, I'm going to call it SP0. Initially, they tested on human skin cells. They use cells from donors aged between 1 and 87 from both sexes and various ethnic backgrounds. as well as AC3. They also tested against standard clocks such as hva, grim age and dunadin pace in aged human skin and lung cells when the genes were applied for 2 weeks. SP0 reduced the transcripttoic age by 4.52 years compared to 5.46 for six years for OSKM where transcripttoic age is the age of a cell based on which genes are active measured by analyzing the gene expression patterns. SP0 reduced scinessence markers by 28% more consistently than OSKM in skin cells for 6 weeks. SP0 reduced the Horvath clock by 7.42 years. The authors also tested the degree to which the cells moved towards pluropotency which was of course much high in OSKM. Meanwhile, the SP0 cells firmly retained their identity as skin cells. SP0 reversed epigenetic age by 13.6 years in caratinosytes even stronger than its effect in fibroblasts that is the skin cells. Delivering one gene is also much simpler than delivering a cocktail of them as building the AAV is less complex. Doing is more straightforward and figuring out the mechanism of action is also easier. In summary, using SP0 brings the same or better rejuvenation as the Yamanaka factors across multiple cell types with greater safety and ease of delivery and in particular gets around one of the biggest concerns of OSKM which is the risk of cancer. So far the paper is only a preprint and if shift biosciences has not released the nature of SP0 this may make getting it peer review tricky but it is certainly interesting and I will be keeping an eye on it in the future. Thank you for your attention and I wish you all well. [Music] | ↗ |
| 3 | IFAS LIFESCIENCE LIVE - CSIR, UGC, DBT, GATE, SET | INDUCED PLURIPOTENT STEM CELLS I STEM CELLS I CSIR2023 I DBT IGATEI | 4632 | 281 | 23 | 84.7 | positive | 4:45 | New star concept and new star concept we will learn. New star topic is this is induced flu reportant stem cells. And induced flu reportant stem cells we will see the effect of YAMAYAN. Induced flu reportant stem cells are what? This is also a cosmetic cells, which is skin cells. So we convert it into induced flu reportant stem cells. And we use these induced flu reportant stem cells to use different regenerative medicines or therapeutic clothing. Like we have to repair our damaged organ. If it is skin burn, then you get the skin cells taken and the skin of the patient is converted into induced flu reportant stem cell. And then this induced flu reportant stem cell, which is made from skin cells, which is made from induced flu reportant stem cells, is made from different transcription factors and is converted into different cells. Like we have removed the misodermy, like we have removed one of the different cells, then we can convert them into different types of cells and use the IPA cells in regenerative medicine. Which means you have to repair your damaged organ. Why do you have to cure it by genetic disorder? Or we can use different different cells, which can be called organs, can be done bone grafting, skin grafting. So in repair of damaged organ, we can use the IPA cells in regenerative medicine. Now the question is, how do you do reprogramming with the reprogramming? So what do we do directly with the help of the painkillers? We do the reprogramming with the help of the painkillers. So we can do this, when we have this effector of the patient. What does it mean? We have some octopuses in virus, so we have some genes in the effector of the patient. We don't express those genes in those cells. Like octopuses, the three-mic tox-2 and K-lapur. These four EMI factors, we put them in the virus, this virus is genetically modified virus. This virus takes all these genes and expresses them in the same way in the same way. Even when the genes express them, octopuses, tox-2, the three-mic and K-lapur, they are used in the induced flu-reportant stem cells. And in induced flu-reportant stem cells, we use medicine. This medicine was very difficult for many people. That's why these EMI scientists had also been given Nobel Prize for this discovery. Because we can convert our somatic cells into an IPS, and we can use induced flu-reportant stem cells. So, where will the question come? The question is, which gene we expressed in somatic cells? The one that we expressed in IPS cells? So, we have to keep this much. Octopuses, three-mic, tox-2 and K-lapur. And this one is called the EMI factors. But remember, these induced flu-reportant stem cells, which we use in the formation of the cells, and use in the medicine. So, these induced flu-reportant stem cells, how they were in their formation, how they were reprogramming, and how they were using it. We discussed this today. So, in induced flu-reportant stem cells, get all the questions of the question. And if you have any doubt, then you can post the doubt question below this video. We will answer your question and the doubt. And how did you get the answer? You didn't understand the topic. How did you get the answer? You must tell us. So, thank you all and happy learning. | ↗ |
| 4 | Modern Healthspan | Surviving Lifespan Extended By 109% With Partial Reprogramming | 6831 | 383 | 42 | 83.6 | positive | 7:33 | [Music] foreign this is Richard from Modern healthspan partial programming is one of the most exciting Rejuvenation Technologies although it has been shown to rejuvenate tissues one outstanding question is whether it can extend the lifespan of an organism this is what the team looked at in this paper gene therapy mediated partial reprogramming extends lifespan and reverses age-related changes in aged mice please note that this is a preprint so it has not been peer-reviewed yet and one of the main authors is Dr Noah Davidson who has recently been on our Channel where we discuss some of the background to this paper the aim of the study was to see if cellular reprogramming impacts Health span and lifespan recent Studies have shown that three of the four yamanaka factors opt-4 sox2 and klf4 with cmic being omitted have reversed age-related changes in vitro and in Vivo however whether the lifespan of wild-type mice can be extended has not been studied in the study they delivered these osk factors intermittently to the whole body using a viral Vector into 124 week old mice which is about equivalent to an 80 year old person this extended the remaining weeks of Life by 109 compared to the controls and also Health span as measured by a lower Frailty index they also saw a reversing of epigenetic age in human skin cells with the same set of three yamanaka factors I will not cover this in any more detail the results may have important implications for the development of partial reprogramming interventions before we jump into the paper let's hear Dr Davidson describe partial reprogramming with yamanaka factors yeah for our next generation of uh therapeutic targets um I mentioned epigenetics uh earlier and our goal is to re-regulate all of your genes back to an earlier State a very powerful tool for this is to use epigenetic modifying factors similar to the yamanaka factors where you do this partial reprogramming which has been a very hot topic of lately where you temporarily turn the cell toward a stem cell and then let it relax back into its normal cell function people have shown benefits from doing this partial reprogramming I did a had a collaboration with Sinclair lab where they were able to show um rejuvenating effects in the optic nerve from an aav that delivered osk these are three genes that are part of this um reprogramming set that uh that came from the pluripotent stem cell field and our next generation of therapies is taking advantage of this idea that you can re-regulate all the genes in a Cell back to an earlier State and make that entire cell younger and if you can infect enough cells in a tissue the entire organ and if you can infect enough organs in the body the entire person and so our goal is to start with a very specific tissue and show that we can have a large effect on a particular disease and then expand the different tissues and cells that we can get into throughout the body so that we can reverse aging systemically in each individual cell they made a couple of points in the paper which I think are worth highlighting the first is that some previous Studies have used transgenic mice which were designed to express the yamanaka factors in the presence of Doxycycline this has the benefit that it removes the problem of delivering the factors to the cell but is not translatable as we are not going to have transgenic humans so in this case they used aavs or adeno-associated viruses to deliver the genes the second is that it will not be young people who are going to be rejuvenated rather it will be the elderly so it makes sense to try the therapy on aged mice in this case the mice were c57 bl6 J mice 124 weeks old these mice have a median lifespan of 129 weeks in the study they used an aav an aav is a non-pathogenic virus for which the DNA can be changed when the virus is injected it will enter into the cell and produce the proteins based on the DNA that have been loaded into it in this case they use two separate payloads one was the three yamanaka factors opt for sox2 and klf4 the genes were not active all the time instead they were used on a Cadence of one week on one week off throughout the trial to control the expression of the genes they used a system which would Express them only in the presence of Doxycycline and antibiotic one of the viral vectors could detect the presence of Doxycycline which then released a promoter Tre that activated the amanaka factors in the other viral package here are some of the key results this graph shows the survival curves from the start of the experiment with the mice aged 124 weeks there were 20 in the treatment group and 20 in the control group the median lifespan is the time when 50 of the mice is still alive for the control group this was 133 weeks and for the treatment group 142.5 weeks this is an increase from 8.86 weeks of life remaining at 124 weeks to 18.5 weeks or 109 percent the total lifespan increase was about seven percent The Gray Line is for the historical data for this type of mouse from the Jax lab which supplied the mice using the Frailty index defined by Heinz Mill they assessed the health of the mice the treatment group was significantly less frail than the control where a lower Frailty score index is better it should be noted that the study was run by rejuvenate bio who is developing Therapies in this area the paper skipped some details with any yamanaka Factor based reprogramming there is concern over Cancer all they mention on this is that they did not observe any gross teratoma formation overall I thought this was a great first step to show that partial reprogramming could extend lifespan in older mice I like that they used old wild type rather than transgenic mice as discussed with Dr Davidson rejuvenate bio is currently trialing a more targeted gene therapy for specific proteins in the liver with the same aav technology which is closer to clinical trial this overall Rejuvenation is in development for their next generation thank you for your attention and I will speak to you again soon [Music] | ↗ |
| 5 | The Visser Podcast | Dr. Richard Visser | BPC-157 vs. Stem Cells: Which One Do You Actually Need? | 161 | 19 | 2 | 83.2 | positive | 3:00 | BPC157 is not magic. TB500 is not regeneration. They enhance signals. They do not rebuild structure. Tendons have low blood flow. Cardilage has limited repair. Ligaments slow remodeling. Lying speed is constrained by biology. So what happens? They enhance angiogenesis. More vessels, more blood flow. They enhance cell migration and inflammatory modulation. They accelerate. They don't reconstruct. If structures damaged, signaling alone won't fix it. That's where people get disappointed. So when you have a mild injury, signaling peptides work. Moderate, degeneration, PRP, structural damage, cellular therapy. This is where we talk about mesenchymal stem cells. A billical cord mesenchymal stem cells. So regeneration medicine is about matching intervention to biological damage, not chasing trends. So longevity is not a stack. It's a sequence. If you get the order wrong, you're waste years. So what are the foundations here? Sleep, seven to nine hours a day. Resistance training, three to four days a week. Protein, 1.6 to 2.2 grams per kilogram of body weight. Stress control. Without this, nothing stabilizes. Muscle is endocrine, muscle is metabolic, muscle is protective. After 50, muscle preservation is longevity preservation. Hormones. Hormones regulate tissue, integrity, and energy partitioning. Optimize responsibly, not aggressively. Insulin sensitivity, visceral fat, mitochondria. Energy is life. Here you have advanced tools. Fattypes, regenerative medicine. Only after biological stability. Longgevity is not about fighting aging. It's about maintaining system integrity. Muscle, hormones, mitochondria, brain, build the system, age becomes secondary. Thank you. Subscribe, bring the bell notification, invite friends. Let's keep going. | ↗ |
| 6 | Modern Healthspan | Cellular Reprogramming In Practice | Prof Vittorio Sebastiano Intervie... | 2019 | 104 | 16 | 81.8 | positive | 9:46 | [Music] foreign [Music] you've tried in Vivo with human uh no sorry in vitro with human cell types what cell types have you tried have you tried like neurons and heart cells and like all cell types uh we we have tried about variety of different cell types uh really a lot human cell types and human cell types that have been naturally aged in the sense that they have been isolated from from an elderly individuals uh this is very important because aging as we know is a very complex phenomenon uh and uh it cannot be simplified it needs to be study in its in its complexity in my opinion um yeah we have tried a variety of different cell types uh uh dermal fibroblasts that were derived from different parts of the body endothelial cells that were derived for example from harder is or or or veins chondrocytes muscle stem cells mesenchymal stem cells different cells of the of the eye blood cells um and so in all of these instances in all of these cell types era has worked successfully uh and so yeah so we we have been trying a lot of different cell types and I can say that you know the same cocktail seems to be working across uh all of them I I seen that you've you've talked about using the cocktail using era to reduce the age of stem cells rather than somatic cells is that like the correct term for yeah normal cells um so can you talk a little bit so how would that work would you take the stem cells out you make them younger and then you put them back in again or you you make them younger inside the body yeah but both both are are true in the sense that if we if we know how to obviously doing this outside of the body is simpler is easier uh provided that you know how to isolate the stem cells and keep them in culture expand them multiply them and so forth so for example in the case of muscles themselves we have been successful successful in doing so because we know thanks also to another to another um IP that's that turn owns exclusively and that was developed by one of the co-founders of turn Marco Cuarta we know how to isolate the muscles themselves from the from the muscle we know how to keep them in culture we know how to expand them and we know how to preserve their stemness which is their capacity of giving rise to all the cells of the muscle for others for other stem cell types you know this is not possible yet because we still need to understand and figure out how you know this process of isolation expansion proliferation happens because every every cell type every organ is in a way very unique in this in this regard um and so for those for those organs or for those tissues in which we know how to isolate the stem cells we know how to expand them we know how to uh to characterize them this process of X Vivo uh Rejuvenation is probably the the first the kind of the low-hanging fruit in a way because it allows us to Target those cells and put them back into into the organ they they came from but of course the vision is to bypass this this process and being able to to Target the stem cells where they are in the organ in the tissue in the body how do you do that by for example again once you know where they are and once you know their chemical you know the the chemical features of their membranes or their features in general you can you can develop solutions to specifically Target them in Vivo in the in the body this video is brought to you by buy optimizers magnesium is a crucial mineral for hundreds of reactions in the body it impacts everything including sleep and muscle and bone health it is difficult to get sufficient magnesium through our food in our efforts to remain fit and healthy my wife and I frequently exercise after which it's important to recover well and get restful sleep to help us with this we chose magnesium breakthrough from biooptimizer because it Blends all seven essential forms of magnesium into one effective supplement while also using all-natural ingredients and being gluten soy and lactose free it has improved our recovery and Sleep Quality since we've been taking it and we are happy to tell you that by optimizers are offering a 10 discount for magnesium breakthrough two Modern Health span audience just go to www.magnesianbreakfruit.com Modern or click on the link in the description to get a 10 discount with coupon code modern10 thank you for your support so how would that work or would that work in cases where you have long-lived cells like the brain right the brain does not build new cells generally so would you be able to do that or would you have to rejuvenate the existing somatic cells well uh era era has worked successfully in both the stem cells and in the so-called fully differentiated somatic cells um so uh I haven't tried yet we haven't tried yet in neurons right but um I I think actually probably the neurons are from a biological standpoint are probably even um kind of better to targets because since they are post mitotic what does that mean it means that they are not cycling it means that they are way more resistant to pass beyond the point of no return because the point of no return is also a function of the cell cycle the more the cells divide the higher is the chances that they can actually go beyond the point of no return neurons hard cells or any other cells which is uh by definition considered post mitotic which means they do not divide are more resistant to that process of of reprogramming and more it's more unlikely for them to go beyond the point of no return so that means that from a safety standpoint they're probably you know an even better cellular targets to to to rejuvenate with air um so more work will follow but you know it is very likely that actually the neurons and heart cells are gonna be are gonna be even a better Target for for air so my understanding would be that you would have like two different I guess arms ways of doing this so one would be to rejuvenate the stem cells and and this is like the end point where you're aiming for is there one would be to rejuvenate stem cells which which would then repopulate the organ and one would be to rejuvenate somatic cells kind of in situ exactly speaking of rejuvenating organs So within kind of the mouse model how what how far have you got in terms of rejuvenating have you rejuvenated an organ like made a liver a young liver or any if you looked at that uh not the liver but we have done we have done this for example in muscle by which we needing the stem cells of the of the muscle in mice we have shown that we can bring the entire muscle because again the muscles themselves regenerate the whole muscle because that's their function we have regenerated the whole muscle to the levels of a youthful muscle so we did this experiment where we took uh a um stem cells from a 24 months old mouse so 24 months old mouse is a very geriatric Mouse okay it's like a 90 plus years old uh human being okay so we took the stem cells from that muscle we treated them with era for just 48 hours so a very short period of of or a very short treatment and then we transplanted those stem cells into a 24 months old recipients so that you know the donor and the recipient were of the same age okay we could show that by doing so so by treating the age stem cells with error that was sufficient to bring the strength of that whole muscle after the Regeneration to the levels of a young by Young I mean six months old mouse so if you compare the two the two ages it's like bringing back the strength of a muscle of the 90 years old human being to the strength of probably 40 30 40 years old human being which is pretty significant and that was xvivo so bring it up bring it out there was an evil followed by the transplantation indivo into into the animal yeah [Music] foreign | ↗ |
| 7 | The Sheekey Science Show | Rejuvenating the heart – is it possible? (Cellular reprogramming) | 14019 | 763 | 56 | 81.3 | positive | 11:41 | Rose if I only had a heart. So hello and welcome to the Shiki Science Show. Well hopefully you all have hearts. Unlike the port in man from the Wizard of Oz. But speaking of wizards, we're going to be talking about some spellbinding science in this video that will surely get your blood pumping. Partial reprogramming of the heart. Or as the researchers call it, referable reprogramming of cardiac myocytes to a fetal state drives heart regeneration and mice. Cool. So the heart of the study begins with well, the heart, that good old important organ that pumps blood around the body as part of the circulatory system, to deliver oxygen and nutrients and remove waste products. And it keeps on pumping without us even thinking about it. Unfortunately though, the heart is still prone to damage, especially for example from heart attacks, which reduces the functional capabilities of the heart. Not so good. But do we need to worry, can the damage be fixed? Well, to repair damage in the body we have stem cells. Stem cells are cells that look like stems. And joking, stem cells are cells that have the potential to both defied continuously, but can also differentiate into specialized cells. A specialized cell in this case being a heart cell, or cardiomyocytes, the more fancy name. For example, you can find stem cells in the intestine to replace cells lost in your gastrointestinal tract, and skin stem cells that are constantly replacing skin cells lost at the surface. The heart however, greatly loses its ability to repair tissue damage shortly after birth. Now this could be the reason why we don't seem to see tumor formation in the heart, but since the cardiomyocytes can't be efficiently replaced, instead the damage is patched up with the fibrotic scar, and the scar tissue reduces the functional capabilities of the heart. So the ideal solution would be to replace these cardiomyocytes or to form new ones. But how? Well, this nicely leads on to the huge topic of cellular reprogramming. Cellular reprogramming is all about, well, reprogramming cells. Okay, well, if you must know, it refers to the process of refreshing a cell's identity. So like a skin cell has the identity of a skin cell, it does what skin cells do, and so converting a skin cell to something different would change the identity of the cell, and the another way of thinking about it is you reprogram that cell. And what has been shown now in numerous studies is that the identity of a cell can actually be erased. For example, the Nobel Prize winning work by Shunya Yamanaka showed that fibroblacells could be reprogrammed to become pluripotent stem cells. So going from a specialized cell to a stem cell, and this happened when the cells were given four factors, opt-4, sucks-2, c-mic, and k-l-f-4. These are more commonly referred to as the Yamanaka factors, or OSKM, as I may refer to from now on. Another phrase I will probably use in this video is the differentiate, the opposite of differentiation, when you go from a stem cell to a specialized cell type. So the differentiation is the reference of this process. Although here, they suggest that the differentiation is more like partial reprogramming. The cardiomyocytes can acquire the ability to replicate like a stem cell and like cardiomyocytes in fetal hearts, but they haven't completely lost all of their differentiated features. As cardiac cells possess special features and have a certain structure that enable them to perform as cardiac cells and get your heart contracting. But this structure is not suitable for a cell to defide, which is why you need this differentiation process to enable the cardiomyocytes to replicate and to potentially repair the tissue. So, would it be possible therefore to regenerate the heart? Could these Yamanaka factors be used to replace or reform new cardiomyocytes? Well, this nicely leads us back to this recent research paper that tried to further explore this. So, what they needed to achieve was to get these heart cells, these cardiomyocytes, to replicate by entering mitosis. Due to much published data so far on the Yamanaka factors, this seemed like a logical approach to follow. Though they were also interested in testing why the reprogramming would work without CMIC since this factor is a cancer oncogene. In other words, in some cancers, this protein is overactive. So, this would just leave OSK. And before going straight to infevil with the mice, they first tested whether they could get cell cultured issues of the cardiomyocytes to grow. However, neither Mika-Lone nor OSK was able to co-acidase these cardiomyocytes to replicate. So, they had to stick with OSKM. But there are other tricks that they can use to mitigate against the potential tumourogenic effects of CMIC. One is controlling timing of the expression of these factors, i.e. when they get activated and for how long, or maybe that's already two things, and then thirdly, they can control the dosage how much CMIC is going to be expressed, so whether it's a little amount or loads of it or some are in the middle. So, how do they actually test all of this? Well, they use a genetic mouse model that only expressed these factors in cardiomyocytes when they were given doxycycline, so it was an inducible system. And so, because they could induce it with this drug, they could time when these factors were activated in the mice. So, firstly, they just did this in normal mice, and six days with doxycycline showed signs of de-differentiation, such as the presence of smooth muscle actin, suggesting that the expression of these factors were having an impact. However, pro-longed exposure shows more complete reprogramming, showing new plasms, cancerous groves, after 21 days of expression. And these groves could even be maintained, even if the mice stopped receiving doxycycline. They also tested pro-longed expression, but with a lower amount being expressed, so with a weaker continuous expression, however, they still saw new plasms by seven weeks. So, the data so far suggested that the degree of cardiomyocyte de-differentiation and proliferation depended on when the expression occurred and how much expression that was. So, so far, pretty much followed what we thought. You have to be careful regarding how much of these factors are expressed to get just the right amount of reprogramming before a cell loses its identity completely and goes out of control. But, does this partial reprogramming, the short-term expression, have any benefits for repairing the heart after damage? Well, as I mentioned, they were studying mice, and to see how the OskM factors could repair damage in their hearts, well, they had to induce some damage. So, they follow a protocol whereby they can induce myocardial infarction in the heart. And to test how the factors could help with repair, they expressed the factors over six days prior to the event, one day after the myocardial infarction or six days after. And in each of these conditions, they gave the mice the doxycycline for six days, so to have that kind of partial reprogramming. So, effectively, we have pre-treatment, acute treatment, or therapeutic treatment. And in all cases, they saw that the amount of scar tissue was reduced when there was expression in over of these cases compared to the control mice. And they saw it improves cardiac function in the mice treated with doxycycline before and during the myocardial infarction. So, it seemed at this point that either the pre-treatment or the acute treatment was best in terms of heart regeneration. As they point out, adults cardiomyocytes improve left ventricle systolic function after myocardial infarction, particularly when reprogramming is initiated as early as possible. So, it's important to point out that what happens in this case was partial reprogramming, which is the potentially safer alternative to full cellular reprogramming, as it enables the reversal of cellular age of cells without them fully losing their identity. Now, you might be thinking, Yamannaka discovered the factors years ago, why is it taking so long to get to human therapies, why are we still looking at mouse models? Well, numerous reasons, but three main reasons, safety, efficiency, and effectiveness. As we've just seen in this research paper, it was only the short term application of the factors, a partial reprogramming approach that was most effective and appeared the safest for the mice. That is, no cancerous graves. As you can see nicely summarised in this figure, continuous expression of the Yamannaka factors caused complete de-differentiation and the development of cancerous graves. And prolonged expression caused irrefutable de-differentiation, such that the cells' identity was erased and they couldn't effectively mature into adult cardiomyocytes that were needed for the damage repair. It was only the short term treatment that caused irrefutable de-differentiation that enabled the cells to partially reprogram and enable the adult cardiomyocytes to re-enter the cell cycle and regenerate the cardiac tissue. Now, many challenges lie ahead. This was done in mice. How long exposure would be safest and most effective for humans? Is there a way that this can be done without semit? The fact that is commonly overactive in cancer. What would be the best delivery of these factors into human patients? Obviously, if both targeting and tight dosage needs to be carefully assessed, this may pose many challenges for human translation. As identification of molecular thresholds that promote de-differentiation but avoid a point of no return will be critical to engineering and safe therapy. But what is most exciting is that there is evidently regenerative potential. And lastly, it raises the question of whether partial reprogramming could cause de-differentiation of other post-mitotic cells such as maybe neurons. And so maybe in another video we can help out the scarecrow with this brain. Anyway, I hope you've enjoyed this video. Leave a comment, always keen to hear your thoughts and if I like it, I may even give it a heart. Anyway, that's all for this video. Thank you to my Patreon supporters and thank you for listening. | ↗ |
| 8 | Dr. Daniel Pompa | DO THIS BEFORE SPENDING $10K ON STEM CELLS | 1990 | 111 | 14 | 79.8 | negative | 15:37 | I'm on location. Oh gosh, wait to you here. This conversation we're having. This is one of the number one things We can do to anti-age and it helps a lot of different health conditions I'm just gonna bring you into the conversation. I really want to focus in on this topic of plasma Foresis what it is. Let's break it down. You're doing really some Amazing stuff here groundbreaking things and a matter of fact if I look a little puffy It's because I just got plasma Foresis. Yeah, so tell them what that is. Let's start there. Yeah, so What you have done was the first step there a pure plasma exchange TPG and so today we put you in the machine and pretty much filter through the plasma to throw it away Mm-hmm. Then we put your blood back. Yeah That is the first step of removing So the oil the red blood cells come in the machine separates right and takes the plasma off separate We throw that away because that's a 60 year-old plasma Me and then and then you know obviously the red blood cells are pushed back in and you are Very healthy like I know you know your blood work, but even then There's just the accumulation over time. Yeah, and there's like a Age program decline. Yeah, and we accumulate senescent products cells that live too long ages In a lot of these inflammatory markers these build up over time right people without a immune to have all these markers Right, you know allergies to allergies. Yeah, antibodies and when you take the plasma off those things go away Right. Yeah, so it's kind of clean out the system And then allow your body to make new fresh one is it is easy of Comparison to say it's like getting your oil changed. Yeah, yeah, yeah, yeah, yeah, yeah, yeah Just exactly that just removing the dirty oil. Okay, so you had you know a laser remove and then tomorrow We're gonna remove another leader And that will be almost all of your plasma a little bit less. Yeah And then we're gonna be putting in young plasma young plasma last the next step. Okay, we take the old off We just kind of said why that's so beneficial and anti-aging just in itself right and then putting new plasma in Why we're doing that? Yeah, so it turned out in Last month especially last month young donors 1825 is almost like the peak of forming for human. There are a lot of Good stuff including hormones peptide sickly Asian and Most importantly, it is loaded with exosone and exosone from young plasma. Yeah, the signal and the instruction Okay, exosomes I just I'm an artist to tell you people like what that means stem cells produce exosomes To kind of signal healing right so you're saying that that plasma is loaded with these signaling factors if you will Cell factors that drive the body into repairing things right and I the way I think of it exosomes kind of like the active ingredients of stem cell so they are they're what actually responsible for all the amazing actions of stem cells They're not cells, but they they they carry the signal Tell the cells what to do yeah, the instruction and in this case Young plasma has exosome that kind of give the instruction for the cell to have young again I have to say that like you know one of my concerns was Okay, I want young You know young plasma, but what about the the health of the donor? Yeah, you know they look at plasma from Young people Would different lifestyle and it turned out the benefit from young plasma those benefits They consistent The individual lifestyle so that's kind of surprising one of the things that you do here is You know how people know the vampire facial or you ever heard of a vampire facial where you take your own plasma If you will PRP right it's not as strong as what would come out here, but anyway And then you microneadle the face and you put that on right well you do it with this younger plasma Right, so you do the face so talk to them about that because that's also not only we putting it in but we're gonna do the face too And I haven't had that done you guys, but we're gonna do it tomorrow. So I You're I'm a big fan of Take care of your own health as a whole internally, but also appearance Like if you look at yourself in the mirror and you happy perfect, but for me if I have options to look as good as I can in a natural way I'm gonna do all of that. Yeah, me too Yeah, yeah, and to respect how I feel and how I look respect my body and This is a great option because again, it will give the signal for the skin To regenerate. Yeah, this give the signal to the skin to regenerate because as we age We're the lower the signaling of factors via you know, vibrant via bolstem cells goes down But these signals that we're talking about that we're getting from plasma goes down as well So a lot of the repetitive injuries that we get um It's because of that we don't have as many of these signaling factors that my 18 year old son had how long did the results last? I mean, like after you get it in you like is this happy is this the benefits go for a week? You know two weeks month two months, so it's months months and it's all depending on the individual as well If you have decent skin or if you've been you know, out in the sun your life and there's a lot of damage Then it will take longer and sometime more treatment to get to the level that we really want to um, so In general, I think everyone if you can do it once a year The a great way to maintain and even to reverse The aging of your skin now someone coming to get that they just come in get micro needle and then you have done Her young plasma that you use right so it's pretty easy actually yeah, so I mean like everybody could get that done now To get to where you take your own plasma off, you know, you have to be connected to a machine for an hour So I mean that you know, that's a little bit different. How long does that healing start? So after you get the young plasma in yeah How is it similar months? Yeah, so when we do that Systemically From my own experience Patient report feeling better surprisingly pretty quick even like the next days a week and typically A sense of mental clarity cognitive improvement more energy those are the first improvement and then you know better join And so as time goes on then the joint starting because healing's happening healing takes time and right the signal the heal for your body Does it go on for like I know for stem cells most tell me if I'm making a good comparison. Yeah, so most of the healing starts It takes like two months a lot of it's three and four months is where you get your highest peak of healing. Is this very similar? Uh part of it, but there's these immediate improvement. Yeah, yeah, okay all the signal from the Exosome okay, yeah, young plasma But then there's delay improvement that accumulate over time okay, and typically the sicker you are the more aggressive I recommend and so you can repeat the process in four to six months to do this for longevity Purpose every night months to once a year Impossible. Yeah, or you know whenever yeah, you can okay, so you mentioned You know chronic cases. What kind of conditions have you seen great results with so you know the uh the initial study for young plasma Uh exchange was done as Stanford where they used this same protocol for patient with Parkinson disease and Onzyme where dementia oh well, and it's her now a It's a very well tolerated procedure And safe and be And uh it shows that people have improvement in their daily function cognitive function and so based on that the golden gift study is kind of kind of and what else to show you were so now it shows people with congestive heart failure There's improvement in the ejection faction how strong the heart squeezing People out immune condition we know that I have had people with auto immune get plasma Frisus and it was like it was game changing for that And not one of the persons they get it done every six months and it'll like keep some symptom free Right, and then we see people with uh, you know lines and more Where they even when they've done you know multiple session Acculation because that is another option But it just take a very long time. This is like much quicker to remove all the bad things and then On top of that you give the body the signal to You know to promote stem cells to work Yeah, because that that's the thing. I mean, you know, I'm 60. I have stem cells of course, right? But a lot of them just needed the signals. Is that right? Right? Right? Yeah Exactly and then they start working here, right? And then it turned out Age related there's the signal the suppressed genes right yeah, and that it's they suppress the bad genes So from taking the young it's signaling the bad genes to be put down. That's important. That's it right and as we age there's also suppression Of the good genes right and now when you have that remove That inhibition or suppression is removed so we will turn on the good genes right and then the young plasma has the ability to turn off the bad genes That's amazing. Yeah, that's amazing. God. Yeah, it's exciting. Yeah, and see and one more and just Various improvement. I have the privilege to see already healthy people that you know go to the next level Wanted to live longer and optimize and then at the same time. I get to see sicker patient and at least able to provide option and and we see improvement. Yeah, yeah I mean, it's we're in an exciting time. Yeah, and to be able to do these things and have these things now You're going to start also carrying these things called self-factors I can't you do with one of the scientists on that and you know where you're putting even more of these signaling factors After the bad ones are taken away. So there's actually even a I don't know what to call it amplify even from and I'm a believer in that. Yeah, stacking everything. Yeah possible because I think that's how the body works right we just kind of like a interconnected system of multiple pathways and organs and and in order to be optimized We just need to um um address everything and the weakest thing is what gonna get you so we just need to it's true You know, and I think that What excites me about this is it's using a natural way of healing. We're signaling what's already there We're waking up your body's ability to heal right that gets a little sleepy as we age You know, and that's the key here and so you know, I Research and I have to have like full Conviction in whatever I offer so personally I've gone through as I share what do as soon as last week I had another round of yeah, yeah, I know I had like That's right when I when I met you I'm like okay, I just want to do everything you do you like to plasma free says normally I will Yeah, and last week I had two vials Self-actors. Yeah, I want to share that with you. Yeah. Yeah, yeah exactly. I'm getting these self-factors in tomorrow as the the young plasma comes in Then we're gonna put the self-actors with it or after whatever you decide that Yeah, I'm so excited for that. Yeah, and then as you've already experienced we combine a lot of Modalities that you already know yeah, but together. It's just yeah, you're doing red light on me You were doing PMF. Wow. I was doing this today Right and the hydrogen I have a little blue around my mouth. Kiss you. I made it with a drop with methylene blue on you were doing all kinds of stuff Yeah, and then tomorrow we're gonna do the IV and R equivalent so it's like the precursor of NAD. Oh, yeah Well tolerated this is what you get when you come here Yeah, and We met recently, but we clicked and I just really love all of your belief in teaching and You know now I get to know you and your family you guys really live what you preach and that's really important to me Yeah, and we can always you know even you you want to optimize I do yeah, no, I mean I was sick and you know, I do I'm Admittedly, I have a PTSD about being sick again, you know when I was sick I always said to my wife, you know, I I don't fear Donning because that was when I was sick That was an easy way out. I feared living my life like I was yeah, and so that said I don't ever want to go back You know, so yeah, I want to live long healthy I don't want to live long if I don't do it healthy. I watched my father. Yeah, do that You know and his saying was Speak it just as he did he said some of a bitch about it. No, no, I was gonna live so damn long I'd have taken better care of myself. Yeah, the thing I want to add is even if you a big fan of them So you plan on doing that. I think Removing at least removing your plasma before doing something will allow the cells to be in a much healthier environment Yeah, I signal and ideally and I do offer like Yeah, yeah I go Yeah, and I mean in doing a big IV of stem cells It's gonna be very expensive. This is a cheaper way to do it. So yeah, all right We'll tell them tell where they find you Dr. Connwen superstar, but tell them so we at Austin region dot com so Austin all egen dot com And the name of the practice is Austin reach out as a therapy in Austin. Yeah, so love love To do what we doing. Yeah, and it's a privilege to be able to You know have option for people who's interested in optimizing life Awesome. Well listen, it's it's a pleasure in an honor to be here I was I was but on I mean I just I'm so excited I just was just so so incredible excited to Impress you and take your health even to the next level. Why not? I'm gonna tell everybody Stay tuned or the next doctor pump a podcast always something new. We're gonna live long healthy and we're doing it naturally | ↗ |
| 9 | Modern Healthspan | Practical Aspects of Cellular Reprogramming | Prof Vittorio Sebastiano... | 1467 | 85 | 18 | 79.8 | positive | 10:37 | In a more general case, so like the topic all on the screen, on the skin or something like that. So how often would you need to do this therapy? Because you're resetting the age of the cell, which one would assume would then last for a while. Is it something you're going to have to do often or once every few years or how often? Well, we don't have yet a definitive answer to that question. It's going to depend on the cell type. It's going to depend on the tissue, first of all. It's going to depend on the feature, the aging features of that tissue. And it's also going to depend a lot on the targeting efficiency that we're going to get. So just to go back to what we said before about the stem cells, if we're able to target the stem cells and make them younger, the stem cells have the long term capacity of regenerating the tissue. So that means that if we can target specifically the stem cells, we have a very, very long duration potentially just with one with one single treatment of the effects of that of that treatment. If we cannot target the stem cells and we target only the somatic cells, then depending on how long the somatic cells survive in that tissue, you may have different timing outcomes. In the case of the brain, and right now I'm just speculating again, I don't have data in my hands. In the case of the brain, since a neurons theoretically is there for for lifetime, if you can rejuvenate the neurons by let's say 20, 30, 40 years, I don't know, you probably gain 20, 30, 40 years in terms of function of that of the neuron. So again, it depends on the cell type, it depends on the tissue, it depends on the disease. But there is there is potentially a very, a very long or there is a chance for for a long lasting effects. How deterministic is the point of no return? And if you deliver like the therapy to three times, I mean, there's a probability that one cell will get hit three times and one cell, some cells won't get hit at all. Right. And so is there a danger that one or two cells would go, would be would go beyond the point of no return? There is there is a chance, yes, there is a chance. And that's why we absolutely need to conduct very rigorous safety studies and develop the appropriate models to study this important question. For example, we have never done experiments as of yet of repeating the error treatment over or pulsing the error, the error treatment over the course of several weeks or several months, we have only done a specific intervention of a certain number of days, which changes depending on the cell type, but we've done it only once for for two or three or four days. We are now doing studies in that in that in that regard. So we're trying to pulse the error treatment. So those two, three or four days, multiple times over the course of weeks to see, you know, what what you if what you were saying is true. And the first one is that by really understanding by really knowing the biology and the physiology of the cell type you're dealing with in depth, we can actually figure out even different windows of intervention or different modalities of intervention over the course of time. Again, just thinking out here, it could be that maybe the first time you have to treat you have to treat the tissue for five days and then maybe the second time just for a couple of days, why because the cells now are rejuvenated in the way, maybe they're more prone to the point of no return, but at that point, the effect that you can get with a much shorter treatment is much is much more effective. So there is a lot, there is a lot of potential interventions, but the bottom line is that we really need to rigorously understand the specific cell type, the specific physiology, the specific pathology and then base, base our base our findings on base, our decisions on on on data. This video is brought to you by bio optimizers. Magnesium is a crucial mineral for hundreds of reactions in the body, it impacts everything including sleep and muscle and bone health. It is difficult to get sufficient magnesium through our food, in our efforts to remain fit and healthy, by a wife and I frequently exercise, after which it's important to recover well and get rest for sleep. To help us with this, we chose magnesium breakthrough from bio optimizer, because it blends all seven essential forms of magnesium into one effective supplement, while also using all natural ingredients and being glued, soy and lactose free. It is improved our recovery and sleep quality since we've been taking it and we're happy to tell you that bio optimizers are offering a 10% discount for magnesium breakthrough to modern health fan audience. Just go to www.magnesiumbreakthrough.com slash modern or click on the link in the description to get a 10% discount with coupon code modern 10. Thank you for your support. The reprogramming sounds pretty wonderful, I mean being able to make that tissue younger again. So is there anything that it doesn't cover? I mean, if I can rejuvenate my tissues, my liver or whatever, so will there still be pieces of me that are going to be getting old? It's an interesting question. So, well, the rejuvenation process doesn't mean that now the cells are no longer capable of aging actually. So you're just bringing the cells back in time, but the aging process in a way that is going to is going to is going to take the clock is going to start ticking again after that rejuvenation process, right? So I think that's that's inevitable. That's really part of our of our biology and our our physiology. There is there is a lot of other things, of course, they need to take it to be taken into consideration. So, for example, we are still not entirely sure and probably wouldn't be a good idea for example to reprogram senescent cells or fully senescent cells because those cells are senescent for for for a good reason because they carry major genetic defects, chromosome operations, translocations, mutations and so on. So it would probably be a good idea, at least that's the way we think about it, it would probably be a good idea, a bad idea, sorry, to reprogram those cells and bring them back in time because they you you potentially would engage them again in some processes of development that would lead to unwanted outcomes. So in that case, for example, one potential solution would be to for example to first clear the senescent cells will kill them somehow in a in a specific fashion, and this is where, for example, the senolytics are are going to be very helpful. And then once you have clear them, then you can reprogram and regenerate the the remaining the existing the resilience cell types in the in the tissue. So that's that's one way of thinking about it about it. The other thing that we have shown, for example, not being changed by by by era is any genetic feature or any genetic mutation that has been accumulated by by the cells. Of course, you know, if a genetic mutation has has happened has occurred, there is nothing error can do in that in that regard. Telomira Tricin, for example, the shortening of the telomira is something that also era is not capable of of reversing unless it's it's a stem cell. Why? Because somatic cells are not capable the somatic fully differentiated cells are not capable of elongating the telomeres. They are kept they become capable of elongating the telomeres once they become stem cells once they go beyond the point of no return. And as we as we said, we do not want to go beyond the point of return. So a quintessential feature of fully differentiated somatic cells is not being able to elongate the telomeres right. And so that's what something that era doesn't do just because of the just because of the fact you know of how error works. Does so what about mitochondria does making the cell younger also help the meaty country. Yes, yes, absolutely. We have we have studied is in a couple of different ways. So we have looked, for example, at the the amount of energy that the mitochondria generate. With or without era. And we have seen that era leads the cells to having more functional mitochondria that are capable of generating more more energy for the cells. My to conjure generate energy also at the expenses of production of the so called reactive oxygen species. So these are oxidative molecules that are detrimental to the cells. We have shown that not only era can lead them to generate more energy, but they generate more energy generating less oxidative stress in the cells. So both of the things are actually very very good for the cells and are triggered by by error. | ↗ |
| 10 | Dr Adeel Khan & Eterna Health | A New Era for Regenerative Medicine in the U.S. #shorts | 1610 | 71 | 7 | 77.1 | positive | 1:01 | So for those of you who didn't see RFK tweeted about stem cells and peptides and if you are their alternative medicine Modalities that I don't know if I necessarily agree with but it's interesting nonetheless And I think obviously my area of expertise is regenerative medicine And so I am excited about the possibility of doing these Therapies in the US without FDA scrutiny now is gonna be a double-edged sword because Joel Rogan tweeted and retweeted RF case Posts and basically tag waste to well waste to well offers mizankamo stem cells from inbilical cord tissue Which are not FDA approved and they're still offering them in the US But now obviously things may change and they may be allowed to offer them legally But mizankamo stem cells as we've talked about most of them don't survive in the body and Most of them don't actually regenerate tissue. They just reduce inflammation and there's no standardized cell population This is why we're using mute stem cells because it's a standardized cell population So I think it's exciting for the possibilities, but we still have to be careful not to let commercial interest | ↗ |
| 11 | Animated biology With arpan | IPSC | Induced Pluripotent Stem Cells Explained in simple terms | Clin... | 7932 | 232 | 29 | 76.2 | positive | 12:50 | Video will talk about induced pluripotent stem cell. Induced pluripotent stem cell is a type of stem cell which is artificially derived from non-pluripotent somatic cell. And this was discovered by Shiniya Yamanaka and his colleagues. So, Shiniya Yamanaka got the Nobel Prize in Medicine and Physiology in 2012. And this is for the discovery of the factors that can convert any cell type into a stem cell. So, these factors or set of transcription factors which are known as Yamanaka factors has the capability to transform somatic cell into IPSCs. So, these transcription factors are opt 4 socks to seamyk and KLE 4. So, the key features of IPSC is they are pluripotent. So, they can give rise to 3 germ layers. They have the capability to form ectoderm mesoderm or even endodermal derivatives. They are self-renewing that means they can proliferate and has the capability to differentiate into specific lineages. Now, let us try to understand how researchers can make the IPSC in the lab. So, obviously, these kind of conversion of any cell into a stem cell requires reprogramming. And this reprogramming can be by integrative methods or via non-integrative methods. In integrative methods which were old school, retroviral or lentriviral vectors were used to give these transcription factors into cells. Now, in non-integrative methods, sendivirus or epizomal plasmids are used. So, problem with integrating method is there is a risk of insertional mutagenesis in that case. In case of non-integral method, it is basically preferred because the chances of incorporating a mutation is less. And it is preferred in clinical settings. So, let us talk about the first experiment that happened. So, there was some mouse fibroblast and there were viral transduction of these factors, oct 4, oct 3 or oct 4, cemic, sox 2 and k-lef 4. Now, after the transfection process, after the transduction process, these transcription factors were misexpressed. They are not supposed to be present in the mouse fibroblast, they are artificially expressed in that cells and eventually the cells get converted. And they converted into something called induced pluripotent stem cells. These stem cells has the capability to generate mesoderm lineage, for example, blood, muscle, etc. It can give rise to a total normal lineage, for example, neuron. It can give rise to endodormal lineage, for example, pancreatic endocrine cells. So, these IPSEs open the door for humongous clinical applications. But question is, how at a fundamental level Yamana ka factor can do these transformation? These transformations are quite difficult, right? To imagine. So, let us try to understand what really happens when Yamana ka factors are added. Inside the cell, the DNA is compacted in form of chromatin. There are many locus which are inaccessible for general transcription factor. And that is why in differentiated cell, other kind of lineage markers are not basically present. So, basically the nucleosome is tightly wrapped around his stone preventing the access to the nucleosome. But Yamana ka factors are very different. They are known as transcription factors which are pioneer transcription factors. So, they can access the chromatin even if the chromatin is condensed. They can latch onto the heterochromatinized regions and eventually open the chromatin region. That lead to transcription of many gene. For example, KLA4, Oct4 and Sox2 give rise to the transcription of Nanog, ESRRB and Indoginus Sox2 and Nanog gene. So, all these locus get opened. Now, overall there is an important process. So, there has to be suppression of the somatic gene and there should be activation of the pluripotency gene network. So, when a somatic cell is getting converted into a IPSE at fundamental level, somatic identity is decreasing over time and the stem cell like identity is gained over time. So, obviously somatic gene regulation networks would basically be down-regulated whereas the stem cell gene modulatory network would be up-regulated and that would be in action. So, question is how suppression of somatic identity happens or activation of pluripotency gene takes place. It turns out factors like KLA4 and CMEK prevents specific fibroplast-specific genes such as coal 1a1, thai1, etc. CMEK on the other hand promote the metabolic or biosynthetic shift that means generally the cells prefer oxidative phosphorylation to generate ATP. But the metabolism now shifted towards glycolysis and CMEK actually up-regulates enzymes and molecules that are required for orchestrating glycolysis, making the cell very much like a stem cell in terms of metabolic needs. Now, all these Yamannaka factors can recruit epigenetic modifiers and many of these epigenetic modifiers are histone-modifying enzyme. For example, it can recruit HAT for adding H3K27 acetylation which would open up certain region of the chromatin. It can also recruit HMTs or histone mithyl transferases. It can give rise to H3K4 tri-methylation which is activitory in nature. Then, DNA-D mithylases can also come into the play and can be recruited by these co-transcription factors. And this would remove mithylation from pleuripotency genes and make this circuit of pleuripotent genes active. They also help to erase repressive marks. So, all these things lead to a dynamic shift into the chromatin architecture. In short, the chromatin of that somatic cell eventually becomes more like a stem cell chromatin. And that lead to the production of genes and machineries that are important for maintaining pleuripotency or a stem cell like state. So, it all boils down into the chromatin and how Yamannaka factors can alter the chromatin architecture. Here are the quick discoveries that really change the field of stem cells. So, first embryonic stem cell was actually discovered in 1998. From that time, one of the big shifts was 2027. So, in 2007, what happens is Yamannaka and Takahashi actually found out that one can use these four factors to convert any cell into a stem cell. Though they got them Nobel Prize in 2012, this was a turning point. By 2010, the first clinical trial of stem cell therapy took place. By 2017, IPSE derived retinal cells were used to treat macular degeneration. So, these are the landmark discovery in clinical perspective. But what are the clinical applications of IPSEs? Let us devote some time on that. So, first, IPSEs can be made from any patients to understand the disease pathology. IPSEs can be used for gene therapy, we just heard about the macular degeneration treatment. IPSEs can be used from the patient for grafts. For example, there is a third degree burn, there is a skin graft required, patient's own cell can be converted into skin cell and can be used as a graft. And lastly, it can be used for precision medicine and it can be used for screening drugs and testing efficacy of the drug. And it kind of creates a tailored treatment strategy. So, macular degeneration is a situation where the central part of the retina, which is known as macula, is getting affected. And it generally happens in the old population. In 2017, the first IPSE derived retinal cells were actually transplanted into the patients with macular degeneration. And this is led by Masaut Akahashi, a pioneering ophthalmologist and a clinical stem cell researcher. She took skin biopsies from the AMD patients, converted them into IPSEs using the Yamana ka factor. And eventually, she grew RPE or retinal pigmented epithelium cells from these IPSEs, because IPSEs has the capability to grow any part of these different three different lineages. And these RPEs were injected into the retina of an patient. And guess what? The patient was actually cured. There are other applications of stem cells and stem cell therapies. For example, a patient is facing a third degree burn. So, a graft can be added into that region. But many of the cases, graft is rejected. Recovery happens when their grafting is proper. So, in order to avoid the immune circumstances, one can literally take the skin cell from the patients and create IPSEs and make artificially a layer of monolayer of skin cells. And artificial skin can be grown in the lab. And ultimately, it can be grafted. In that way, the own skin graft would not be rejected. Now, there are other applications of stem cells. For example, studying the human brain. A developing human brain is very difficult to study. Scientists use monkey and mouse brain to understand what really goes wrong in human brain and how human brain develops. Human brain develop is challenging because this is not possible to access the human embryo and manipulate the human embryo in the mother's womb. So, scientists have discovered something called brain organoids. And these can be made from the IPSE cells. So, IPSE can be converted into brain-like structures known as organoids. And this has been used to uncover many diseases. In the lab, basically, IPSEs would be dissociated and aggregate would be formed known as embryoid bodies. These embryoid bodies can be guided through morphogens to differentiate into specific lineages and an organoid would be formed. Using this strategy, scientists like Maddling Lancaster found out what goes wrong in the patients with microcephaline. So, skin cells from microcephaline patients and a typical individual was taken. And it was found out that the brain organoids develop differently. In the patients with microcephaline. And this was one of the landmark discovery which used the IPSE technology to understand how brain development goes wrong in many diseases. So, overall, we looked at the induced pluripotent stem cell and its application in medicine and biology. So, I hope you like this video. If you like this video, give it a good thumbs up. Don't forget to like, share and subscribe. See you in the next video. Bye. | ↗ |
| 12 | Business Insider | Scientists Are Closer Than Ever To Reverse Aging. How Does It Work? | ... | 654006 | 13746 | 2799 | 76.1 | positive | 14:01 | imagine if you could turn back the clock to reverse aging get rid of wrinkles gray hair or see 2020 again well there's a handful of startups trying to do exactly that and billionaires are pouring money into this hoping the tech will be developed before it's too late for them these Tech billionaires they they like their lives a lot and they just don't want to give it up so they're driving a lot of this scientists are trying to manipulate human cells to rejuvenate your body body it's a technique they're calling cellular reprogramming and it could be reality in just a couple of years I'm an apologetically afraid of dying if you cure aging and and people have the mortality of young adults then they would live thousands of years but how does this work should we worry about side effects and how close are we really to cheating death I'm Hillary brick and I'm a health correspondent here at Business Insider aging is as inevitable Progressive process of loss of viability and increase in vulnerability so once you reach about age 30 your chance of dying doubles roughly every 8 years and you see that across populations from poor countries to wealthy countries it doesn't matter that's very consistent across populations but to understand aging we need to think about how it all starts because we start out in a much different more flexible shape picture a fertilized egg the single cell where we all be begin that cell could become anything it's what we call a stem cell stem cells are versatile and can turn into any type of cell your body needs and then as they develop the stem cells become more specialized scientists might say they're differentiated cells but really it's kind of like they're getting job titles like a skin cell or a brain cell or a hair cell our stem cells are like our body's built-in Rejuvenation system they're constantly turning over making new stuff for us keeping our body going with new hair new skin fresh neurons these stem cells are required for regenerating tissue because our tissues you know our cells die and have to be constantly replaced that's why you know when you fall down and and get a bruise it quickly repairs itself as we age the number of these stem cells decreases and their efficiency declines so our body has a harder time repairing and replacing tissues and this leads to slower healing and more signs of aging all over aging is really an accumulation of changes a lot of it is chemical damage and eventually things start becoming dysfunctional that buildup of damage over time as we age creates problems some scientists think of it kind of like a photocopier or something like where the more copies you make the more worn out it gets and the more little glitches and errors it has on it this damage in our DNA is kind of like glitches in our human programming over time the errors cause issues because our bodies use that code to make the proteins that sustain our whole life and fight infections and Thrive as people when the instructions for our cells are damaged they stop working properly which is part of what happens during aging so when scientists talk about reprogramming what do they mean so this idea of reprogramming is could we take cells that are fully differentiated like the skin cell or muscle cell or whatever and program them to go backwards to the stem cell that originally generated them or even you know make them somehow biologically younger the idea of reprogramming your cells to slow down aging is not that new in 2012 a Japanese scientist and former surgeon named shin yamanaka won the Nobel Prize for his Discovery yamanaka figured out that you can use four special genes to reset your cells back into stem cells and that set of four genes are called the yamanaka factors they contain instructions that can reset a cell back to an undifferentiated State making it like new again essentially rewriting the cell's program and guiding it back to a more flexible stem-like State this was a big deal for aging science these newly reset cells known as induced plur poent stem cells can then turn into any type of cell you need and could potentially be used to grow new tissues or organs like younger skin or a new heart typically when researchers do cellular reprogramming in the lab they use an inactivated virus to inject the Amo factors it's pretty much the same technique they use when you get a vaccine so you have essentially have a virus and what is virus does that he has those four factors and it transports them to the cells and you know they have to be regulated so you don't want too much of it not too little so you have to get it right but at least in animal models this is possible to do now in 2006 yamanaka showed this can be done in mice then in 2007 the next year he started on human cells first with skin and his experiment was quite successful what scientists and some startups are trying to do now is to partially reprogram some cells so they act younger but don't go all the way back to being an embryonic stem cell again it retains its identity it remains a liver cell or a brain cell or a skin cell but it's rejuvenated and so that's that has a lot of potential because if you can rejuvenate cells without them losing their identity that's what you want but even if these kinds of treatments become available it wouldn't be like an 80-year-old can suddenly turn 20 again maybe it could be rewinding that receding hairline ditching arthri is regenerating heart muscle after a heart attack or healing neurons in your retina so you can see better as you age I personally would love it if they could regenerate uh cartilage uh in my joints you know at my age that would be great and also if if while they're at it they could also regenerate hair you know so that would be a billion dollar multi-billion dollar Discovery if you could safely regenerate hair and bald men okay they're even loftier goals like curing Parkinson's regrowing parts of the brain or rejuvenating your entire body if you have a young brain it doesn't develop Alzheimer's or dementia anymore so if you can turn your brain young you will make you resilient to diseases maybe even you will treat and cure diseases we don't know so that is the promise of the field is that if you make your organs younger they'll be more resilient to diseases now most of these ideas are in the testing and research stage and not available as treatments to yet but some scientists are close I chatted with Johnny Huard who's restoring joint cartilage for elite athletes using their own stem cells we take your bone marrow that contains stem cells and we reject that into your knee he's also experimenting with one form of cellular reprogramming using so-called epigenetic drugs which can change the way our genes behave in some cases making them act younger again we have used cells from old people they came in we took the cells came in the look that their epigenetic expression was going down use epigenetic drug to bring this back up and the cells look younger so would you say that that's a form of cellular reprogramming then what you're doing with those patients yes it is a form of cellular reprogramming because what I did is I Arvest St from you take drugs to regulate your epigenetic expression and make those C younger so I rejuvenate your C but so far this treatment is just lab work it would eventually require FDA approval to put the reprogram cells back into people's bodies I'm not saying that you know this thing will never be approved 3 years from now but is not approved today but the potential of this technology has sparked Visionary ideas about the future I imagine a future where children or or babies even before they're born they're engineered not to age or at least engineered to be resistant to diseases like Alzheimer's disease if you cure aging and and people have the mor ality of young adults then they would live thousands of years you could still die of course but you wouldn't have this exponential increase in mortality recently we've seen an explosion of research into this area and money is flocking into cellular reprogramming and other longevity treatments Jeff Bezos for example is an investor in Altos Labs Altos is a pretty secretive startup based in California that has recruited some of the most elite aging scientists in in the world the company has at least $3 billion in funding another big deal longevity scientist is Harvard Professor David Sinclair he's behind a bunch of different longevity companies but he has experimented with cellular reprogramming already on mice and monkeys and he's hoping to do people next for example he conducted an experiment with two Mice from the same litter same DNA they're like twins except one is biologically older now because it's had its DNA manipulated to act older mimicking the stress that a body goes through as it ages then Sinclair's team says they use cellular reprogramming to restore the old Mouse's organs back to a more youthful state for example they found that they could safely reverse age related blindness and rejuvenate the kidneys and the muscle in the mouse Sinclair started a private company called life biosciences it's raised at least $175 million so far they're going to get this technology into people's eyeballs and cure age related blindness he says the ey injection will be ready soon maybe within a year or two but it remains to be seen how quickly it can actually move from Labs into clinics and there are other people you may know of who are investing in cellular reprogramming too you really think what it's like if um Sam Alman the billionaire behind chat PT is also gunning for cellular reprogramming he's poured $180 million into his lity startup retro biosciences I interviewed the CEO of of retro biosciences and he told me they're trying a slightly different approach to Cellular reprogramming take the cells out of someone's body then reprogram them and pop them back in he thinks it might be safer that way the field is maturing because people and investors and Rich folks think that there's going to be uh commercial outputs in it that they'll be able to make money out of it that means that we're going to be able to have a product from the field which is what I want people love to that aging is going to be solved and we're all going to live healthily for a very long time but the reality is biology is kind of complicated tweak a gene here insert a new program there and you'll likely kick off multiple other processes in the body including some that could be harmful and may not be immediately obvious either mice have benefited from this kind of reprogramming but to go from there to ask you know can we now start using this in humans it's a long stretch and the reason is that we would want to make sure that over decades you know it's not going to increase the risk of cancer what's the point of living an extra 10 years if it's going to cause cancer increase the risk of cancer before that the point ramach Krishan raises here is important in the early days of using yamanaka's reprogramming technique scientists often saw that cells they created could form teratomas which are a type of tumor this happened because because two of the four genes used in the reprogramming process are enogen enogen are genes that can divide indefinitely and that poses a cancer risk always keep in mind that an immortal cell is a cancer cell so the big danger of partial reprogramming and cell Rejuvenation and reprogramming itself is cancer so we actually know from studies in mice that if you reprogram the cells a lot in a mouse they become cancer and obviously you don't want that so there is this this balance you have to achieve you want to do it in a safe way that allows to rejuvenate cells without turning them into cancer there's also a chance that continuously expressing these yamanaka factors could lead to liver failure or make your intestine shut down and there may be other toxic effects we haven't even considered yet I think for several years now we've seen like the Silicon Valley billionaires trying to go after the medical field and pretty limited success one of the most stunning and memorable failures in recent memory was probably the blood testing company th which ended up basically being a total sham these Tech entrepreneurs CEOs business people and billionaires have all been really successful in the world of computing technology and it seems like they're trying to take this very same technological approach to what are very complex poorly understood biological problems so it remains to be seen if you can reprogram a person like you would a computer but it's an idea that's attracting a lot of money and a lot of scientists I think it's wonderful that there is more activity there's more interest and there's more investment in the field it's just so that there's more potential curing aging would be a Monumental achievement and it would be a huge um change in in medicine in health care in society and I think there would be magnificent and a huge Triumph of civilization [Music] | ↗ |
| 13 | SciShow | The Rise and Fall of Stem Cell Research | 240022 | 9641 | 401 | 74.4 | negative | 7:36 | You know how great TV shows often take you on a journey with twists and turns leading to an ending you never saw coming? Signs is like that sometimes too. Consider the case of IPSCs, a kind of stem cell researcher that was going to revolutionize cellular therapy. After years of clinical trials, that failed to happen. But as luck would have it, IPSCs ended up advancing completely different fields. Just a little background. Each cell in your body is optimized to perform a highly specialized role. Your neurons have long-thin structures called axons to carry electrical signals. Your red blood cells don't contain a nucleus, so they have more room to carry oxygen. Each cell also began as exactly the same thing. A humble stem cell with a potential to become anything. We used to think that once a stem cell had become specialized, a process called differentiation, that was how it was stuck forever. But a surprising discovery in 2006 by Japanese biologist Dr. Shinya Yamanaka changed that. His team used modified viruses to deliver 24 genes into adult skin cells. When the viruses entered the cells, they hijacked the cellular machinery and inserted their DNA into the host DNA. When these cells were left to grow, they became something else entirely. They now looked and behaved just like the stem cells found in embryos. The team tested combinations of the 24 genes until they were left with just four that were necessary for the reversal of an adult cell back to a stem cell. Those four genes created a type of protein that controlled if and how much of other genes were expressed. They changed the genes expressed in an adult skin cell into something very similar to an embryonic stem cell. The researchers called these incredible new cells, induced pleuropotin stem cells. Or IPSC. Sleropotin C means the ability to turn into almost any other type of cell. IPSC's were immediately seen as a major breakthrough in stem cell biology. And researchers believed they had incredible medical potential. Just imagine an unlimited supply of specific cell types to repair an organ or tissue that wouldn't be rejected by the patient's immune system because they came from the patient. And to top it all off, IPSC's could be made without the tricky ethical issues that come with using stem cells from embryos, which had been the basis for much stem cell research up to that point. The first clinical trial kicked off in 2013 with researchers making IPSC's from the skin cells of patients with macular degeneration. A condition where damage to the retina leads to loss of vision. The IPSC's were differentiated into retinal cells and transplanted into the eye of the first patient, whose vision improved. But the excitement that had been building over these cells was short-lived. The IPSC's generated from the second patient showed unexpected mutations. Due to safety concerns, the trial was immediately halted. Now, that initial failure wasn't all that surprising. Knowing that it can take decades before a scientific breakthrough results in something that people can actually use. But in the 16 years since IPSC's were discovered, there has been little progress on that front. Changing enough adult cells into IPSC's for cellular therapy turned out to be difficult. And genetic mutations have been a problem in subsequent trials. As of 2021, only 19 clinical trials have taken place that transplanted IPSC's into patients for therapeutic reasons. Of those, only one has advanced to the final phase of testing. But that's not the end of our story. Although research into the use of IPSC's for cell therapy stalled, they would soon lead to incredible advances in other areas. In those applications, the potential for genetic mutations or the technical difficulties of producing enough cells for use on humans weren't a problem. As we mentioned, IPSC's are very similar to embryonic stem cells. This has allowed researchers to create embryo-like structures that mimic the early stages of human development about two weeks after an embryo has been implanted into the uterus. These structures are organized into the three layers of different cell types that give rise to tissues and organs. They can be used to study the incredibly complex biological processes of early development like organ formation and the development of the nervous system. Hopefully, this will help us understand why things go wrong during that stage of development like heart defects that are present from birth. Until IPSC's came along, we weren't able to study things like that due to an international policy that says embryos can't be used for research more than 14 days after fertilization. And it doesn't stop there. IPSC's can also be used to study diseases in addition to take Parkinson's, for example. At a time it's diagnosed, most of the patients dopamine-releasing neurons in a critical area of the brain called the substantioneigra are already lost. Researchers have made IPSC's from the skin and blood cells of patients with Parkinson's using similar methods to those we described earlier. This has allowed them to grow an abundant supply of that kind of neuron, study why they're dying, and even test potential new drugs on those cells before moving into clinical trials. In the future, this might lead to more personalized medicine where your IPSC's are used to test what treatment works best for you. IPSC's are even on their way to tackling organ donor shortages. Cells generated from mice have been inserted into rat embryos, which were genetically edited so the rat could no longer grow a pancreas. The mouse IPSC's filled the empty niche, growing into a pancreas. In theory, we can use the same technique to grow human organs in animals like pigs. But we're not quite there yet. Human IPSC's have been successfully incorporated into pig embryos before, but in small numbers. So there are a few more kings to iron out before we can grow a full custom organ. In 2012, Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for his discovery of IPSC's. At the time, IPSC's were promised as the future of cell therapies, but their true value was unexpected. They've changed how scientists approach many other aspects of biological research forever. Like that TV show with the Wicked Twist, IPSC's have delivered a satisfying ending no one could have predicted. I can't wait for season 2. I also can't wait for this month's SciShow Space Pin, and you shouldn't wait because it's going away at the end of the month and will never come back. The November Pin features near shoemaker, a NASA mission designed to meet up with an asteroid near Earth. And when this pin is no longer available at the end of the month, there will be another one for you, specially made for December. And what do you do with these pins you ask? Put them on your fancy new pinboard. You can find a pin and pinboard at dftba.com slash SciShow and the link in the description down below. They come separately or bundled. Thanks for taking a look. | ↗ |
| 14 | Dr. John Tait | Stem Cell Therapy for Joint Repair, DOES IT REALLY WORK? | 19225 | 562 | 97 | 74.3 | neutral | 13:34 | Is stem cell therapy the future of joint repair? Is it hype or is there a lot of hope around this topic? I'm Dr. Fontaydom, non-surgical orthopedic specialist and that's what I want to dig in today to answer this question here. Is stem cell therapy a bunch of hype or is there hope around these emerging treatments that, but they've been using stem cell therapy in the US since the early 2000s. We have a lot of data on this and if you search PubMed which is a search engine for public scientific literature, you'll find hundreds of not thousands of articles at this point in regards to stem cell. Okay, now in orthopedics we're looking at this for a few very directed aims, one of the most common ones being near-thritis. So if we look at worldwide disability, near-thritis is going to compromise more people than just about any other condition combined after, say, low back pain and compared to other conditions like heart disease and diabetes and cancer and we kind of roll those up. If we look at the amount of disability in the duration of disability that people have from arthritis, it's staggering. And so it's one of those solutions, or it's one of those problems we need better solutions for. And what a lot of people are seeking me out as a non-surgical orthopedic specialist is to get there without surgery. So I wanted to dig into a little bit of the science around stem cells. First, talk about some basic science of what stem cells are. Then pull some of the recent literature to try to answer this question. Is there a lot of hope here? Is it still a lot of hype? A lot of, you know, kind of marketing and other things that some companies may put out there in the space? But what is the real science show on this? What am I seeing in my clinical experience and my practice now doing this stuff for more than a decade? So first of all, if we look at stem cells, you know, if we take a stem cell and first go to the basic science of what stem cells are, well, there are cells that are made inside the bone marrow of our body. And stem cells are called mesenchymal and pluripotent, and that they can differentiate into many different cell types in our body. And they can help grow new tissue. They can regenerate old failing tissue. And in fact, more than a million cells per second in our body die out and they're replaced by new cells every day. So if we look at this concept first, stem cells can come from really two banks in your own body. So we call that autologous, meaning from you. They can come from your bone marrow and they can come from your fat tissue. Okay. So in the U.S., most of the treatments we're using are bone marrow derived. And some people are using fat tissue derived stem cell. And those are the two things we can take. That's really where we can access stem cells from one's own body. Pierp on the other hand, which I've detailed in other videos is not a stem cell. So Pierp stands for platelet rich plasma. And platelets are cells within your blood. So if we do a standard blood draw, we're going to get platelets. Platelets have growth factors. Inside of stem cells, we have packets of other growth factors. So when a stem cell encounters a problem in the body, okay, it's getting a chemical signal back this way. Because our body communicates, cell to cell chemically through the signal. So if we have a distress signal over here that attracts a stem cell to the environment, then we're going to get a release of these little packets of stem cells stem cell growth factors with instructions on what to do. So it's pretty cool. So this releases those growth factors in the environment where there's that failing tissue. It helps to recharge and regenerate the body's own healing potential in that environment to stop the degeneration and turn over their cells a little bit faster in that environment. So in the case of a knee joint, like I have here where we have arthritis chewing away at the cartilage in one's cap of cartilage on the end of the bone here, as that is breaking down, the body is getting signaled for reinforcements. It needs a resupply to help battle against that degradation and that degeneration that's there. So when we look at stem cell therapies, this is the ability to take stem cells from elsewhere in your body and replenish the supply of cells that are needed in the failing part of your body. So most commonly where we take these cells is from the pelvic bone, we call the ilium, the back of your hip bone. And through a local block with anesthetic, we're able to punch a little hole through the bone and aspirate the bone marrow. And from there we get stem cells. Okay, we get a lot of all your blood cells are made inside the bone marrow, but after we take what we call that aspirate, we're able to concentrate it down and get the fraction that is mostly stem cells. And it's that fraction that we want to put back into the environment, the failing joint, say a knee arthritis situation where it needs a resupply to help things heal. So very simply, that is what stem cells in the U.S. that's how we do it. Another country is they can do other things than what we can do in the U.S. where they can grow those cells out and they can replicate them and make larger banks and supply those cells to return to the patient. But in the U.S. it's all same day. I can take your bone marrow out, I can concentrate down to the stem cell fraction I want, and I can inject that back into you via precision injections with ultrasound or x-ray guidance to place them back into the joint or into a ligament or tendon or whatever we're treating. So then if we go over to, you know, the the hype versus hope, I want to bring our attention to an article that was done by a French orthopedic surgeon, Philippe Hurnigel. In 2021, he published this data, okay? But this data, they were tracking for more than 15 years at that point. And it was a very well done study and a very interestingly done study in the fact that what they did is they took 140 patients that qualified to have joint replacement, okay? So 140 patients is what they started with. Of those 140 patients, they randomized them to get joint replacement or stem cell, okay? So they had knees that were comparable in their pain. They both required joint replacement, okay? And these were patients that were 65 to 90 years of age. So what he did in this study is he took an aspirate of their bone marrow just like I shared a moment ago. He replaced the one knee, okay? Randomly, they selected which knee was going to be replaced and which knee was going to get stem cells at the same time under anesthesia while the person was getting their joint replaced. They put stem cells in the other side, okay? And then they followed these patients out and they waited and they waited and they waited because this study, they followed people out for 15 average follow-up was 15 years, which is remarkable in a study because three to five years in a lot of studies is a long-term follow-up. But they followed people out for 15 years. So they published this in 2021, but they started tracking these people back in 2006. So what they found out in this data, again, they replaced one knee on the patient. They put stem cells in the other knee on that patient and then they let them go for a while, a long while. What they figured out in the latest follow-up before they published this data was pretty staggering that when you look at who crossed over, okay, to get joint replacement, it was only 18% of the patients, okay? So the patients that had stem cells, they needed a joint replacement, okay? Metal criteria for it, they had high rate arthritis that put them in a position in knee joint replacement, but instead they got stem cells, okay? Only 18% of those people crossed over over that follow-up period to get the other joint replaced. That means 72% of the people that had stem cells placed in their knee never crossed over to get the other knee replaced, which is kind of mind-blowing to think about when the norm, what we see with people, is the knee starts to fail. They get treatments like anti-inflammatories and when those fail to get improvement, then they make it cortical steroid injections put in the knee. And when that fails, maybe they get HA hyaluronic acid injections put in the knee and when that fails, eventually, they get joint replacement. So again, these people were already there, right? They needed joint replacement. They were 65 to 90. These weren't young people, but this was a great model of real life when what these people wanted is a higher quality of life. They want to be able to, this was a study is from France. So people there, maybe they walk a little bit more than people do in the US. They walk to the grocery store, they carry things home, they go up a flight of stairs, they walk the dog, they want to get on the ground, play with their children, ride their bike, maybe play around a golf, something like that. So their outcomes that they were looking for were really realistic and that's real life. You know what most people are looking for is realistic. Sometimes people come in looking for things that are unrealistic, like we're going to inject stem cells and it's going to repair all the cartilage damage in their knee, which isn't going to happen. So we want to catch things on this slide down the hill. If somebody is at a high grade of arthritis, you know, our outcome data is obviously less good and as far as prognosis of first front end success and then duration of benefit. But if we can catch somebody in that middle act, okay, and intervene with stem cells, then think of it as a halting of this progression. It shuts off this chemical process that's looping, it shuts off pain and allows people to get back to function. And ideally kind of holds this downhill, what we know is this downhill progression towards joint replacement. But this to me was really just a landmark study and I had the honor and privilege to sit in a room a few weeks ago to conference and listen to them present this data because he's now I believe 80 years of age. He did his first joint replacement when he was 50 years ago. He did his first joint replacement. But he got attracted to this concept of trying to figure out are there other ways they could help people without doing surgery. And so again, a study like this 140 patients 15 years of follow up and only 18% of those people ended up getting their other joint replaced. After getting stem cells as a pretty convincing argument that stem cells have a place here in treating orthopedic conditions like joint arthritis, knee arthritis, which is very prevalent condition. As I mentioned, it's one that's going to impact many many people over their lifetime. And the treatments we have available to us look joint replacement is transformational when you can replace one's joint and they're up walking around on it that day. I mean, that is remarkable on itself. But what is even more remarkable is maybe we don't need to do that. Maybe we don't need to do that as early or as to as many people as that study showed it had a great benefit for pain reduction functional improvement elevating that person's quality of life and giving them really what they wanted, which is the outcome to have that function without surgery. So I think, you know, there is to sum this up today. There's a lot of hope around directionally where things are moving with stem cells. Obviously different countries, different rules, different regulations, different things they can do. But he's done studies on this for a very long time in a population there in France to publish this data and really collect it or very long period of time, which again, the deficiency in a lot of studies is maybe the numbers aren't big and subjects I looked at or the duration of them following patients wasn't great. But this kind of hit the mark on both of those. So I think it's very encouraging. I think there's a lot that can be explored here. It's why we've used it in my practice personally for over 11 years with our patients with a good amount of success, particularly in near arthritis. When we look at it for hip arthritis, shoulder arthritis, other conditions like partial rotator cuff tear, it has a roll there. So if you're sitting there watching this and you have those conditions, you may want to be thinking about these treatments. I would recommend you do find somebody who's qualified trained competent to do these in your area in the Tucson area. That's where I am. But we'd be happy to look at that information you have around the joint, the state of it, how severe is the condition? What is your functionality currently? Where do you want to be? And is this the right match treatment? So in summary, I don't think this is hype. I think there's a lot of hope here. I think there's a lot of work yet to do to really get to a point where we know empirically, what do we need to do with each case to have more success? And on the flip of that, who's not going to have success? And we know what some of that criteria is already. If somebody's got a joint that's declined so much, it's angulated. They don't have full range of motion. But if you have full functional range of motion, your shoulder and your hurt, we know that these treatments are very, very successful. At least in my hands and the hands of a lot of my colleagues that have been doing these procedures for well over a decade in the US. So that's the short summary on stem cell therapy is where they sit today in 2025 in this country. What we can and can't do with yourselves. And so if this helped you in any way, click the like button so you get more information like this when we publish it here out of my practice. If you have comments around this topic specifically, drop them below so that we can make future content to answer those questions for you. And subscribe to the channel so you'll know every time we post up a new video. | ↗ |
| 15 | The Sheekey Science Show | Can CRISPRa solve aging? | 14010 | 581 | 38 | 74.3 | positive | 11:02 | now i hate to say i told you so but i've just said it and while i always knew there was much potential for using crisp activation for cellular reprogramming and now we have a paper that suggests in more detail how and that it's very effective so hello and welcome to the cheeky science show where in this video we'll take a look at this paper crisp activation enables high fidelity reprogramming into human pluripotent stem cells and a deep dive into crispr crispr activation and also cellular reprogramming so firstly before we go any further we just need me to explain what cellular reprogramming actually is and well let's go back to 2006 when shinya yamanaka published the now landmark study whereby the introduction of four factors the yamanaka factors oskm which when expressed in differentiated mouse cells could reverse them to pluripotent stem cells these are cells that have the potential to divide continuously but also to differentiate into different cell types so they were termed induced peripotent stem cells and so this is where the reprogramming comes in because you effectively alter you reprogram a cell's identity now i've made a few recent videos on cellular reprogramming but i think it's important to reiterate why there is much interest around it and there are three main reasons firstly for disease modeling for example if you wanted to study neurons of an individual instead of taking their actual neurons which would be quite challenging to do you could instead derive them from a stem cell and get that stem cell from one of their skin cells using this reprogramming technology secondly you can use it to understand the biology of cell states and also cellular plasticity how easy and difficult it is for cells to be reprogrammed by chemistry nerdiness and then lastly for rejuvenative regenerative medicine approaches so the common method of reprogramming is giving cells the genes encoding their reprogramming factors such that they are overexpressed however having this forced expression of ectopic genes can cause the following problems of target gene activation so you're expressing genes that you don't really want to be expressed which potentially could be due to having a high concentration of these reprogramming factors that may bind to dna or they wouldn't otherwise secondly it can result in heterogeneous reprogramming and that can result in two different outcomes besides having a stem cell as the best case scenario when you're doing reprogramming is to well achieve free programming but you may also cause a cell to die it may cause the cell to become senescence or it may become transformed and cancerous not so good but why does this happen and is there any way to make this more controlled and safe and so on from this the cells that do become stem cells may be aberrant so what is normal cellular reprogramming and how does crispr help well once these yamanaka factors are expressed the assumption is that they will then activate other genes and the downstream consequence of these events results in a cell changing its epigenetic landscape and stabilizing into the stem cell states so what would be desirable features for reprogramming technology well i would like a reprogramming technology that matches my personality reliable efficient safe with a good sense of humor okay we couldn't scratch the good sense of humor but anyway reliable we want to know it's going to reprogram and not do something weird e.g not die or become senescent and also we don't want the cell to try get halfway and go that i'm not going you want it to fully commit and i suppose tied into this as you want it to be reproducible you want it to do the same thing every time and then efficiency reprogramming can take time the cells need to make some serious changes you might think slow and steady is potentially the best approach you know you can't rush great art but maybe a longer duration also means the sale was more likely to go off track so maybe shorter is better and then safe which uh given my recent by accident this probably isn't a personality trait of mine though i do sometimes wear my lab coats anyway safety goes back to what i was saying with reliability we don't want the cell to become uncontrolled and cancerous we want to know that it's trustworthy so crisp activation now almost a year ago i told you about crisp activation even though it's been around for much longer than that but essentially it's a modified version of crispr so conventional crispr you have a guide rna that recognizes a specific site on dna and then you have a protein that binds that guide cas9 class 9 this protein has the activity to cut dna and make a double stranded break you can then change the sequence of the guide rna and target the crispr complex elsewhere in crispr activation we mutate cas9 so that it doesn't cop dna but it retains that site-specific binding activity and also you can tag cas9 with other small proteins that promote transcription so expression of genes and so what would happen is you target cas9 upstream of a gene you want to express so let's say the yamanaka factors and it can activate gene expression so that's why it's called crisp activation um so the key difference is that this is so called endogenous expression not ectopic and it's actually been done already before using the four yamanaka factors so oct4 sox2 klf4 and mick plus lin 28a and the motif express no genes expressed in early development that they call eea but the thing was this crisp activation approach had pretty low reprogramming efficiency so not really fulfilling my personality checklist so this brings me on to the new publication where they conclude that these findings support the use of crispr a for high quality pluripotent reprogramming of human cells so how did they do it and are there advantages or disadvantages to the crispr approach over these more conventional ectopic gene expression approaches so to speed up their discovery process of other potential target sites they use the system that enables reprogrammed cells to be easily detected and analyzed so their approach involves using cells that grow in suspension but then attach to the surface of a plate when reprogrammed by doing that they identified the most efficient reprogramming when they had extra eea targeting and when they targeted the promoter of mir-32367 this latter thing is still a gene but instead of creating for a protein it cares for a micro rna i don't have the time to go into all the details as to like how these are expressed or why they work but i did make a video a few years back with more details if you want to learn more but like with the activation of the yamanaka factors which are transcription factors that can regulate the expression of multiple other genes micrornas can also influence many different genes and so you get much bang for your buck but one of the rationales for these specific micrornas is that they reduce the expression of some factors that repress reprogramming so you're repressing the repressors anyway with this extra eea targeting and the micro rna targeting they called their technique crispr a plus me it's getting very personal today but me here stands for the micro rna sites they're targeting and e for the eea metis anyway that was a cancer cell line but they also showed that it worked in human fibroblasts and crispr plus me was the only reprogramming condition that properly induced induced pluriplated stem cell colonies from fibroblasts derived from an 83 year old man and this is a cell line that's known to be difficult to reprogram and so the cool thing that they also did in this paper was that they did single cell rna sequencing to see the gene expression profiles of the cells using this approach compared to a transgenic approach what they observed based on the gene expression was that mid reprogramming so around so day 15 the crispr a plus me cells looked more like the reprogrammed cells than the other transgenic approaches suggesting that the kinetics of reprogramming were also being enhanced so that's how but what are the advantages of using this crisp a well as i mentioned earlier you're expressing the endogenous genes and you're modifying the epigenetic landscape in situ and by having this endogenous instead of exogenous expression you also retain extra steps of gene expression such as splicing and regulatory elements which may also influence the control over the expression of these factors which might be useful from a safety perspective and then the second thing with using crispr in general is that it enables high multiplexing once you've got cast 9 you can just add multiple guide rnas for different sites that you want to target so this is the magical summary figure you start with some differentiated cells add the crispr machinery targeting yamanaka plus more eea and microrna 302 and you get induced pluripotent stem cells i think there's many studies that could be done to further explore this technology i think it'd be kind of cool to see well if they could better map out the chromatin landscape of these cells and also see potentially why the transcription factors the yamanaka factors are binding in these cells compared to the other approaches to further understand you know what is about this approach that seems to be more effective um and then they can link it back to their transcriptomic changes but anyway i'm digressing so can crispr solve aging well guess we'll have to wait and see but whether it's through crisp activation or other crispr techniques i've not mentioned in this video such as gene editing knockout screens or using alternative cast proteins for diagnostics it will certainly aid in our future understanding of the aging process and how best to treat and diagnose for it so with that i'd like to thank myself for making this video and all the cells involved thank you to my patreon supporters and thanks for listening you | ↗ |
| 16 | Joy Kong MD | 3 things you need to avoid if you're getting stem cell therapy. #stemc... | 6925 | 285 | 15 | 72.8 | positive | 0:43 | There are three things that you need to avoid if you're getting stem cell therapy. I'm Dr. Joy Kong, a triple-pore certified doctor, and a stem cell specialist. Number one is eating junk food and any inflammatory food. So that's any food that's full of preservatives, additives, basseed oils, or with high sugar content. Number two is alcohol. You should avoid alcohol because it's toxic to the stem cells you just got and all your other cells. Number three is overexertion to the point where you may damage the tissue that you're trying to repair. I see this a lot in people who are getting injections for joint and tendon repair. They often feel so good after the treatment that they overexert themselves feeling invincible. But in the newly formed tissue, it's still fragile and cannot withstand the same kind of stress yet. Those are the top three things I would avoid if I'm getting stem cell therapy. | ↗ |
| 17 | The Longevity Forum | The Potential and Realities of Partial Reprogramming | Daniel Ives | 364 | 16 | 2 | 72.4 | neutral | 26:46 | [music] Yeah, thanks for the invitation and uh really excited to uh share some of the work our team's been doing. So um just to begin with, why is uh partial reprogramming reprogramming exciting and it's uh because you know fundamental unit of the body is the cell and where is aging coming from? It's coming from every cell in your body. So if we can get to the bottom of aging in a cell and we can cut across the body and to get to all of your cells, we might do something quite dramatic to lifespan. So that's the idea. This is seems to be a point of leverage. Obviously, we need to prove that, but that's uh sort of behind the excitement. Well, I've broken the presentation. Sorry. [clears throat] Thank you. Let's try this. >> Okay. >> Oh, yeah. >> It is a >> Okay. So, I'm going to switch the t I'm going to switch the title up a bit. So, firstly talk about the realities and then I'm going to talk about the potential. So, realities is sort of summary of of what is known at least what is known uh in my head and sort of more broadly in my team. prefer to use that. Oh, >> thank you. >> Yeah. >> So, Shinyamanaka, Japanese scientist who in the mid 2000s discovered how to turn sematic cells or your skin cells into stem cells. And what we didn't realize at the time is that the biological age of those stem cells at the end of this process was zero. So it actually reversed age and so you looking at these stem cells they were remarkable. They behaved like embryionic stem cells and you know embriionic stem cells do have a age of zero. So there was a little bit of evidence uh this had happened but it wasn't until um a little bit later that uh there was a more definitive result. So um Steve Hall back in 2013 discovered uh the multi-issue DNA methylation clocks a very robust biomark with age highly correlated with age in single tissues works across multiple tissues um you know I could talk a long time about clocks I won't for this presentation but Chandra at University of Edinburgh basically took an data and uh applied the clock algorithm to the methylation data. So this blue line is the methylation age of 62y old fiberglass and over a period of expression of about 50 days of young. So you can see uh between 0 and 20 days the clock reversing from 62 years all the way down to zero which at the time was an astonishing result like slowing down aging or stopping aging was exciting enough let alone reverse aging. So at the time this result was published I just disproved the hypothesis behind my company shift I was looking at mitochondrial DNA damage and the clock was not responding to this damage even though we had a therapeutic approach simultaneously chandra showed that not only could you do something about the clock you could reverse it so it's quite clear at that point there was something really exciting going on under the bonnet of yam factors um so why not why not use factors all across the body. Um, let's see what this does to lifespan. You know, why why try any harder? And uh the reason is obvious in hindsight is because these factors were always designed to make stem cells. That's what Shyamanak was optimizing. How do I turn an adult cell into a stem cell? So that was the feature he was optimizing. The bug was rejuvenation. So you got to remember these are poor potency inducing factors. That's what they were designed for. And one of the qualifying assays for chlorotency factor is when you express it in an animal, it creates a multi-tissue tumor called the terterat. This slightly grizzly picture at the bottom. Uh there's a two arrows pointing to two grows that shouldn't be inside the body cavity of that mouse. So I think the bottom line is this is incredibly exciting that you can reverse the age of cells. Um but clearly there's a lot we don't know. um specifically everything about rejuvenation apart from the amanaka factors that's all we know at the moment there's these four factors never designed for rejuvenation but aren't we lucky that we happen to encounter uh cell rejuvenation in the first place so this reversal in cellular age doesn't mean anything beyond the clocks and does it mean anything beyond hallmarks of aging which are also reversed and the answer is yes. So in 2016 a scientist I think on the west coast to begin with called car mante he showed a proje mouse so this is a mouse where you mutate a nuclear lamin to create a protein called projeran where those mice basically show accelerated aging um even in the presence of that mutation if you overexpress young you can increase uh the lifespan substantially so remember the mutation's still there and then you're using an acopat which don't seem to have any direct uh link to the mechanism of action of this model. So you overexpress the balances and you increase lifespan. So I think synthetic rescue might be the appropriate term. Um and it wasn't until much later that this result was reproduced in just physiologically aged mice. So not special projuroid mice that age faster but just mice black 6 J mice that have lived 2 years. Um and it was rejuvenated by it's actually a commercial initiative not scientist or scientists within a commercial initiative. the overexpressed OSK. So this is three out of the four factors but minus the oa gene cate those those three fats were put into an ada virus with quite a broad tropism meaning it can go across lots of the body the idea being try and rejuvenate lots of cells and that would have greater impact on lifespan and they were able to double remaining lifespan according to median lifespan so this was a result that was conspicuous by its absence for quite some time but that result finally came in I think it was two two or three years ago now So these factors can have an impact on lifespan. Uh there are other interventions that impact lifespan more significantly. Um but this does show you there's a proof of concept like if we reverse age we can also impact lifespan and then for any reprogramming these are some of the latest studies. So this is uh again a publication by John Carlos Bonte and he what characterizes a new hallmark of aging which is most of well the identity of most of the cells across your body seems to drift towards fiberglass identity specifically activated fiberglass identity as you get older. So it's quite an interesting phenomenon like this loss of self at least at the cellular level and he shows that partial reprogramming pulls that back. So you've got this new hallmark of aging. He hasn't called it a hallmark, but for the sake of argument, there's a new hallmark of aging and reprogramming is reversing that as well. So I talked about the clock, but here's a new feature and that's reversed. Um David Sincler in collaboration with Jonathan Weissman. He's one of the scientists behind single cell bombing technology. So I take this quite seriously. And he characterizes a downstream pathway of the amateurs which is sort of resilience pathway and basically shows that reprogramming is activating this resilience pathway and that might have something to do with uh benefits in vision loss which is one of these early applications for matters. So that's some of the latest papers. Um so moving on to the potential of partial reprogramming. So um to begin with I just want to describe the technologies we use to find um some new rejuvenation genes. I won't be able to uh discuss this in a lot of detail today. We have a much longer talk. So I'll just discuss those at high level but um I will then move on to the findings which sort of uh they they make the tools more credible. The fact we actually found something in the first place otherwise they just be some interesting tools but they they did actually come together and do something useful. So there's tool two tools and and these are both products of machine learning that I want to discuss. So one is a single cell aging clock. So you might have heard of epigenetic agent clocks. This is a a way to robustly measure biological age but at a bulk level in a like a whole petri dish of cells. You can't look at the single cell level and what's going on with aging. Um so yeah, one of the things I spend a lot of time with my team doing is uh building a big data set of uh lots of different uh fibroblasts of different ages collecting the methylone collecting the single cell transcriptto and with machine learning finding a way to predict methylation age at a single cell level from the transcriptto. So we we have like a proxy of the methylation clock um within gene gene expression. Um so that's tool number one. This is a this that's a product of machine learning a single cell agent clock. Um the second tool is actually uh sort of blows my mind this exists but it does exist. So so we call it a virtual cell. There's other labels for this uh I think self activation model cell simulation but just describe where this thing comes from. So if you take a machine learning model like a transformer or graph neuron there and you feed it single cell data. to single cell transcript data from tens of millions of cells. It learns the relationships between the genes. You know, by looking at enough cells, it can establish if gene A is up, Gene B is down, gene C is up, gene A and Z are down, right? You can look at enough cells and now it understands how genes impact each other. And you can put that in a computer and in silicon you can say, oh, I overexpressed two genes. What's the impact on the rest of the genes? And when you have a single cell aging clock, you can comp you can convert that gene signature into an age. So you're able to do these vast campaigns of experiments. So this on the right hand side is a campaign of virtual experiments. It's about 350,000 experiments would have taken 5 years to complete in the web. Even with a single cell clock, it's about one week of compute. So you can see the the power of having these uh virtual cells. You can basically do every experiment you ever want to do and take the most exciting results effectively from the future by sort of reaching into the future picking out the best result and that's what you get to test. So I think my favorite my favorite line is you can compress three centuries of future experiments into less than one year compute. So it's like getting into the Delorean going to the 2300s running down the gene combination bringing it back home testing it. Those are the interventions we're testing at the moment. So for the whole guide of view um we have change in age of virtual cell along the bottom. So what was you know when we overexpress different combinations of genes what what impact does that have on the age of the virtual cell? So you actually see this peak of 2 and 1/2 years which is an artificial shift to the right hand side because we electrocute the cells in the training data. So we think there feature of acute electrocution. So don't put your finger [clears throat] in the socket. you'll be two and a half years older and but it's a normal distribution on each side of that. So in the green box are pairs of genes that rejuvenate the virtual cell. In the red box there are pairs of genes that age the virtual cell both of which are interesting from a intervention perspective. We might want to overexpress a rejuvenation gene uh or combination of genes or we might want to inhibit proaging genes that might be good for us as well. And clearly inhibition is much easier to do as a drug. Like most drugs are inhibitors. Um and there's just more options in terms of getting to the whole body. So is this useful? Right? That's that's the question. Is it useful? And yeah, the answer is yes. And the great irony of having a virtual cell and a single cell agent clock is that the whole reason we built those tools was to explore combinatorial space. before we have to explore all combinations of two genes, three genes, four genes because the acts are four genes overexpressed together. That's what we know. So we're trying to find something better. Let's stick with what works. Um and the first thing the virtual cell told us were there were single gene drivers across different combinations. So the same gene would feature across different combinations of genes that rejuvenate the virtual cell. And this gene um initially this was a speculative experiment. said let's take this gene called sp0 that's a coping and on its own so this graph in the middle is the change in epigenetic age now these are real cells now in the dish using epigenetic clocks I'm just showing you the most robust clock that we use called the principal components going clock from Steve can with Morgan uh doing a principal component transformation on top of it again I could talk about clocks a long time but it's this is the rob most robust one that we rely on and you can see that GFP we have no change in age over the duration of the experiment which was 6 weeks. So this is constitutive expression over 6 weeks and OSK this is in a bulk population not in a sorted population. Um we rejuvenate 2 and 12 years a single gen trip0 rejuvenating 5 years. So we're it's roughly double the velocity of rejuvenation. Um on your right hand side um this was a key result for us which is we're trying to find safer rejuvenation. So again factors they have this chlor potency inducing feature with that feature. Can we get away from that dangerous activity and uh the answer is yes doesn't come out very well um on this on this screen but uh you have four panels um you see OSK and OSKM you see this white dotted line that's the boundary between white glass on the outside and a colony induced forent stem cells growing outwards. So you see with OSK after 42 days you do see colonies grow OSKM you see lots of colonies as expected but SP0 control you don't see the colonies so we very excited to identify a single gene sufficient to reverse the epigenetic clocks it's not reversing aging right that comes later but at least this is our screening system reverse those clocks and not induce latency so the next question for us was can we rejuvenate different cell types because these are just fiberglass and ultimately we want to rejuvenate as many cell types as possible go across your body and yeah see what happens after that and uh there is a lot of good news in this presentation it's not all good news though um so um I'm showing you two cell types each with four different epigenetic clocks just to show you how robust this single gene is so uh we've got principal component skin blood principal component multi tissue generation H2 and you see GFP OSKS0 and you can just see like robustly we're rejuvenating across those different uh clocks and carrot insights were also robustly rejuvenating across those clocks but a much higher velocity. It's very interesting. This whole discovery system was built for fiberglass. When we try in a different cell type, we were worried about not rejuvenating that cell type. We actually see more rejuvenation in the keratinosite surprisingly. And that seems to be more robust than OSK and keratinosites in the one in two of the clocks. You're seeing a sort of abnormal result with OSK. We don't have an explanation for that. Um, and at this point we've discovered uh 190 genes that impact our single cell aging clock. So 40 in the proaging direction, 150 in the rejuvenation direction. Clearly some of them are more significant than others. Um, and S0 is highlighted on this plot. So this this is basically a way to represent single cell data. Uh, each dot is a single cell. If the dots are close together, that means the gene expression is similar. They're far apart. that gene expression was different. The color of the doll is how uh the age of the cell changed during the experiment. So it's very blue, it got younger. It's very red, it got older. And so in total, we found 190 interventions. We actually we ran a poll internally like how many do you think we'll find? Some crazy guy 150. He wasn't crazy enough. It's great when that happens. You know, it's so so hard to get anything to work fromology. And when when this, you know, when this came in, this was sort of a moment of celebration. Um we found at this point around 30 genes that reverse epigenetic clocks significantly 10 of which outperform RSK. So you see this red dotted line is OSK and 10 genes but individually it's sufficient to rejuvenate the excess OSK. So it looks like rejuvenation is more distributed than we expected and it's not just um exclusive to matter. It seems to be we don't know what the mechanism is, right? But it seems to be more distributed than we expected to begin with. Okay, let me get back to the right slide. And yes, I I'm just going to highlight go back here. So I've highlighted two genes. One is SP0, but one is a proaging gene called SP 101, which originally we overlooked because, you know, we're not interested in making people older, but I sort of talked about maybe we might want to inhibit pro-aging genes because that's more druggable, right? We could develop we're more likely to develop something like a small molecule that can go across your body and impact that type of gene. So, this gene is very special because SP 101 is is widely expressed across the whole body. So this is exciting because if we could do something with this gene, we could impact it across the body. It's only expressed in a few cell types. We can only impact it in the cell types, but this gene is expressed across the body. And more than that, it's actually been used outside shift to impact lifespan and reverse fibrosis. This was the first time the data took us to a specific disease target. Some sort of a big question for a company. How do you birth this new type of therapeutic through a disease focused regulatory path? So yeah, this gene to histo fibrosis and so we brought uh we brought this intervention into our own systems and we tried to inhibit this gene now because when you overexpress it ages itself but is it reciprocal if we knock it down can we rejuvenate and the answer is yes and so we're able to get about one year uh rejuvenation per month velocity by sRNA knockdown of this gene. So it's roughly a third of the velocity of sp0 when you overexpress it. So there does seem to be some compromise. Um and more than this you can sorry this is an 8we experiment so 2 years across um 2 months and we're also able to prevent fibrosis. So we pre-treat cells with an sRNA and we induce fibrosis with tga um uh this this sRNA completely prevents prevents fibrosis when we get it. [laughter] Um >> we just we just intercepted um some external data where some investigators completely um for other reasons looking at SP 101 SRNA in fibrosis showed you you can reverse uh mesh and eroded model. So I've recreated the data otherwise you can trace it back to the author. My company's out of business but but it's it's incredible. So these you know these investigators went into a mouse they reverse fibrosis. Little do they know this is actually a rejuvenative gene. So that's I guess that's the difference between when we're looking at this and say when this investigators are looking at it. So um this this you know this gives us this development path. We were looking for this mouse data. We're actually funding to do the mouse data and then we it's like a gift from the universe, right? Somebody's done it for other reasons and so we're sort of getting a little bit on the back foot. It's like well now what right? We're there. Um so we're going to sort of try sort of mix up what we're doing in the next few months. Um you can also impact this gene target by small molecule. Um so there's a binding partner as a nice pocket and there are molecules that can interrupt the binding of that partner to sp 101 and you rejuvenate slightly less than the sRNA and prevent fibrosis. Unfortunately this molecule is toxic to the second cell type. So as it's not ready not ready for prime time but it does show you small molecules are within the realm of the possible which is exciting right cuz a molecule can get across your body. Uh yeah got got to go fast and there are multiple family members in this triple0 family. Some of some of these family members all of which have very similar protein sequence and many are regenative. One is not regenative. So it's this this pink arrow at the bottom. Um it's it's a very similar protein sequence. It's very different levels of rejuvenation. So we've identified the sequence specific to the rejuvenative family members absent in the non-re rejuvenative family members and we're co-folding every other protein in the genome to that sequence using like an alpha fold type algorithm and we're actually finding a bunch of candidates that we're about to test. I think I'll be shut down. Uh okay just yeah just some feelood stuff at the end. Um next year for us is year of the mouse. So we want to rejuvenate liver want to impact fibrosis although that's happened externally. We want to go into hearing loss. There's lots of evidence that that will be useful to rejuvenation. And we want to impact lifespan but see you know we're outperforming these early assays. What can we do in a lifespan setting? And I just wanted to oh yeah we're going to make these special mice that they're born with the gene inside their body. And the the purpose is if we express this gene across the body is it safe? Because if we developed the molecule and it wasn't safe to get across the body, that would be a tragic way to find out. You know, it's better to say prove prove the safety of this gene immediately. Then there's a reason to develop the molecule and get across the body with a drug. Um so just just some uh notes on the guiding mission. So enrich these gene targets with systemic efficacy and safety, right? So we can get across the whole body. Uh link those systemic compatible drug modality. So we got maximum effect size and then gain maximum traction lifespan. I just yeah I wanted to end on the feel good. So I mean ultimately we want to make this a mundane scenario where it's like the obvious thing to do. These pharmaceuticals exist. Why wouldn't you take them and keep yourself in good shape? You know it's socially irresponsible to do so. Your loved ones would be telling you to do this. What are you doing? Not taking your medicine. Um so this is you know this is on the later half but this is something very exciting and you know one of the reasons we do this. we get up every day and also, you know, just I want that amount of energy and I want to, you know, see these things happen and I want to be able to get, you know, into orbit and you're going to need really good biology to do that. It's a rough ride getting into space and coming back, let alone being old, right? You can actually do some terrible things. So, I think these types of technologies give us the ability to do very new things. We shouldn't forget that and how exciting this is. So, I just wanted to end on that. >> [applause] >> THANK YOU SO MUCH. Wait a minute. Sorry. One quick thing I was going to say is your um your transgenic um expressor um or the don't be put off if you do see something fun or bad dose. So there are lots of things for you over I suppose particularly is it conditional the the transgenic would you be able to switch your body? Yes, it'll be an inducible questioning data. Come on. >> Thank you for that. Um, it's obly really interesting to see stuff getting, you know, down the lineinical maybe at some point. Um I understand the protecting the commercial interests. I'm curious if there is already research out there maybe not looking direct directly at this gene target for rejuvenation purposes but why haven't you filed for some kind of property protection and then you can say what gene target is just to give a bit more scientific validation what you are doing. So do >> yeah I can I can I'll speak loudly. Um so yeah we do we do try to cover our footsteps so we can be um share as much as possible. Um so we do we do have IP on that but there are certain you know sort of meta data around that where someone can there's lots of uh loopholes people can get around things. So it's it's I guess it's in in our interest toocate for the foreseeable future. Um but I can give you some details. So this gene sp0 very conserved almost almost perfectly conserved in mammals also highly conserved all the way to worms. So that's interesting. It flashes in and out well very rarely expressed across the body with the exception of the germ line in early development. So it flashes on and off uh in the germ line in early development. So we don't know what that means but maybe it's maybe maybe it's something to do with this natural rejuvenation event. We can't prove this is causation. it might just be correlation. Um so yeah some interesting features like the conservation and the fat is sort of you know expressed specifically in part of the body which is responsible for resetting age for the next generation. >> Thank you. Thanks. Thanks very much. [music] | ↗ |
| 18 | The Royal Institution | The cell programming revolution – with Mark Kotter | 88590 | 2545 | 169 | 72.0 | positive | 29:22 | [Music] [Applause] thank you thomas um for this kind invitation and a big thanks to the royal institution for having me here to give this talk these are unusually challenging times and the question is whether it's appropriate to talk about science in the context of such geopolitical events this but these events have extraordinary impact now on people and the long-term and positive changes on our societies are often driven by innovation so my background i'm a neurosurgeon i look after spinal cord injury patients partially because i'm curious but also because the tools that i have to treat my patients are very limited i went into research at the moment i have screws and rods that i can put into their spines but there's nothing i can do to give them back the use of their hands or walking so we need to innovate and the thing i'm really very excited about are cell therapies that's the concept of using a cell as a therapy and these cell therapies can replace lost cells but they can also interact with their environment so you can call them intelligent drugs the last wave of innovation however happened in physics at a very particular moment in time when physics transitioned from a descriptive science so scientists were observing and recording to a predictive science a special moment was the introduction of calculus to describe the laws of motion maths gives you a lens to look into the future we can now calculate how long it takes an apple to fall from the tree until he hits the ground and this together with the creation of more and more sophisticated tools sparked waves of innovation from telescopes to steam engines spacecraft and computers and computing again introduced a phase shift since ada lovelace wrote the first computer script we've built computing power that allows software to transform the world but here's the limitation of current computing the hardware determines the software not vice versa but what if the software could determine the hardware what if you could use computer code to control the physical the physical nature of objects it's already happening right in front of us it's called biology so we need to move away from the traditional questions of biology how does it work how is it built and how did it get there to a new paradigm in biology in which a code script is the kernel of biological theory in this paradigm the nucleus is the hard drive it contains the dna and these genes interact with each other to create programs so-called gene regulatory networks the entire space of programs you could call the operating system of a cell and at the core of this is the genetic code this is the way that information translates into the physical reality into protein and here you see a wonderful depiction of the inner makings of a cell and all these different proteins that form molecular machines at the top you can see the nuclear membrane with nuclear complexes they're very long structures they're proteins that provide structure to the cells and then they aggregate to form organelles on the right you can see an energy producing organelle called mitochondria but do we have the tools to program biology well we started doing so about 10 000 years ago when we started to select plants and animals with traits that are desirable and then in the 1700s we learned how to hybrid hybridized plants and today nearly all of the vegetables and grain that we consume have been somehow influenced by us in the 1800s we learned about the concepts of evolution and the laws of inheritance in the 1950s we discovered the structure of the dna and in the 1970s we discovered the first restriction enzyme that's a protein that can cut dna in very particular sites and that allows you to engineer biology so we've used it to generate bacteria that create insulin and insulin is a very important drug now and that treats patients with diabetes in the 1980s the tools became more refined we started to use them to to create plants modify plants in the 1990s we learned how to clone mammals um some of us will remember dolly the sheep in the 2000s we sequenced the human genome 2010 we built very refined tools for engineering dna crispr the molecular scissors that allows you to cut the dna exactly where you want it to cut and we've also learned how to activate programs in cells and i'll come to that so the tools are very sophisticated but what about the maths again sequencing and other omics technologies in the recent years have helped to translate biology into numbers and attending today's conference here at the conference about programming cell identities i learned that maths is really progressing as well i think we're not far off predictive models in maths so for 50 years we've been engineering biology and at the center of this was greg winter sir greg winter engineer developed a technology that allows you to engineer antibody drugs um in in bacteria and this allowed us to create a second generation of drugs so the first generation of drugs were small molecules and like aspirin this second generation is a lot more sophisticated and more recently we also started to program other microbes to produce materials biodegradable materials such as spider silk and have been used in this very high spec running shoes so we've been programming lower species but is it possible to also program higher species like mammals here we need to go back to the 1980s the heydays of molecular biology and you see harold weintraub here who discovered a gene a transcription factor that's a gene that regulates other genes which he called myod and you observe that if you activate that gene cells switch fate they go from a skin cell into a muscle cell that's completely contrary to the dogma of developmental biology so developmental biology is still the predominant dogma in science it's based on the understanding that a stem cell forms the origin of all cells in the human body and in order to produce a neuron or a skin cell it has to differentiate into more and more specialized cell types waddington proposed a model by which a marble you can look at the picture marble running down a valley and it hits certain branch points where he has to choose these are called self-made choices in order to ensure that not one single cell type is missing during development these choices are based on probabilities stem cell biologists are studying the chemical cues that enable us to bias these self-made choices in order to nudge cells down particular trajectories and to create particular cell types there are two problems with this approach number one development takes time it takes about nine months until a baby is born and second these self fade choices there are a lot more of them on the way to become specialized cell types so you're accumulating a lot of probability and chance events and that causes inconsistencies today long protocols with lots of inconsistencies are the major but bottleneck for manufacturing cells and it's the reason why we don't have cells a stem cell based therapies in our clinic yet but harold weintraub proposed a completely different paradigm if a single transcription factor can switch cell fate we have to relearn biology unfortunately harold died 49 years old and his workforce forgotten for nearly 30 years until shinya yamanaka surprised the world with a new discovery which earned him his nobel prize so yamanaka discovered that a combination of four transcription factors is able to program a skin cell back into a stem cell and this stem cell behaves just like an embryonic stem cell so this allows us to create stem cells from every individual each of us has their own repair kit and the second thing it did was take away all the ethical constraints in the use of embryonic stem cells there is no need to chop up an embryo finally this is an early stage he maybe even opened the door to cell rejuvenation now marius wernick was in the audience was inspired by this work and asked the question whether this paradigm can be generalized so he showed that you can take a skin cell and program it into a brain cell and then he took a stem cell and programmed him to into a brain cell and then i have no idea why you did this marius you took a liver cell and turned it into a brain cell in any ways i think this showed that this a perhaps a generalizable principle but there's still a problem with cell reprogramming it's often very inefficient this is also what we found when i started my lab at the university of cambridge and the objective that i had was to program human oligodendrocyte precursors that's a specialized cell in the brain that's really important in repair processes of the spinal cord and the brain so i was joined by matthias pavlovsky a very talented phd student who now has his own lab in germany and within a fairly short period of time he figured out a transcription factor combination that allows him to produce these cells and you can see a beautiful depiction up here the problem was that this was a very rare event about one in a million cells turned into oligodendrocytes so the dogma was you need to refine the transcription factor combination the program isn't right but his data shows something entirely different it suggested that there's a new problem that we were facing called gene silencing so the stem cell recognized that someone is wanting to activate a new program that is inconsistent with their current state and they shut it down so we decided to tackle this problem and for a few years we only made incremental you know change improvements in fact it's quite hard actually um i used nearly all resources that we had we put the credibility of the lab the survival of the lab at stake and we were quite desperate until one moment um matthias called me and showed me the following video so here you see human stem cells converting into brain cells within days so 10 times faster as previously and the incredible thing here was that every single cell in this culture turned into a neuron and these neurons are the brain cells that connect to each other you can see fine processes and then they start signaling electrical impulses and and reach maturities that you haven't seen before so my first reaction is this this is not possible he probably had photoshop this video these students in cambridge are pretty smart so he took me down to the lab we looked at the cultures and it was real so i thought probably the stem cell that we were using was broken um so let's take another stem cell um takes six months he came back it worked again and then thought okay this is a maris vernick protocol i mean this is probably very unique and therefore um this is still a glitch but over the years our lab company and collaborators have been able to show that it works again and again and again for various different cell types now let's look at that if you think about disease every disease manifests at a cellular level so every cell is potentially a treatment or a model to study this disease so the impact of this is quite incredible the way we achieved this was by inserting the genetic program of the cell into specialized locations in the dna so-called genetic safe harbor sites and they protect the cell but they also protect the program from silencing this creates a control system that allows us to switch on genetic programs at will so the cells can't escape and this allows you to create all sorts of different cell types like the neurons that we've just had a look at so the next challenge here is how do we identify the cell type programs that encode each of the cell types every human cell has twenty thousand genes and at any particular moment in time approximately ten thousands are switched on and these determine the function and the identity of the cell of the twenty thousand genes two thousand genes are transcription factors these are the genes that regulate the activity of the other genes and themselves and what we've seen from studies emerging over the past decade that about one to six of these transcription factors encodes a cell identity so every cell has their own unique combination so the question is how do we read this out if you look at the number of experiments that are required um this is pretty large eight point eight times ten to the sixteenths um i've calculated this approximately thousand scientists working for three thousand years that's going to be difficult so we had to come up um with with something else and to do so to think bit deeper about this problem we entered the collaboration with the london institute of mathematical sciences so they were able to show that the way that dna rna and protein interacts in a cell it creates a set of constraints that limits the possibilities and already reduces this by orders of magnitude and we've also been able to refine the experimental approach by breaking down these pools of transcription factors into smaller pools and ways of screening them we're now at a point where we actually can read out all cell type programs in one big effort it's not going to be cheap but it's doable but imagine the impact that this could have so this is a darpa style project and i'm really keen to get this off the ground the next question is how is the cell type actually determined and defined in the genome so there's what intense landscape again and there are really two possibilities on the left you could imagine that a cell is entirely predefined in the genome so it sits in its own little valley and on the right is the opposite hypothesis a cell type is a label that we attach to a combination of sub programs so if the second we're right we should be able to combine programs from different cell types and we again have to go back to the 1980s to harold weintraub's work because he asked that question and he showed that we can combine a cell program of a muscle cell and a pigment cell a melanocyte and he also was able to create some sort of hybrid of a brain cell in a muscle cell and we've done similar things using transcription factors combining a brain cell with an immune cell this confirms that the operating system of cells is created by sub-modules and it opens the opportunity to create cell types that actually don't exist potentially have therapeutic use so then the next question that we always get asked is how close are these reprogrammed cells to the real cells that we have in our body traditional stem cell biology has struggled to produce cells that resemble the cells in our body because often they are stuck in an embryonic or early immature phenotype but if you want to do a therapy or if you want to do research often you'd like to have the mature the adult cell type so this picture up here is a landscape that we've created with data from the human cell atlas so the human cell atlas is a international consortium that is trying to chart all cells in the human body and they're using a technology called single cell sequencing so they can read out thousands of genes in single cells and so if you look at the top these are this is a picture this is a landscape of uh liver cells the cells that you can find in the liver at the top you can see adult hepatocytes liver cells and at the bottom they're the fetal the embryonic early stage counterparts and in the middle there are all sorts of other cell types that you can find in the liver from immune cells to fibroblasts etc etc we can now create liver cells with transcription factors then we can project them onto this landscape and what you can see here for the first time we were able to produce fully mature hepatocytes in the top their fetal counterpart and some of the intermediate stages as well so now we've got about a technology that allows us to program biology what are we going to do with it i'm a medic so my my primary aim is to use this technology for medical applications and the technology that we've created in the lab has been spun out into two companies one of them is bitbio is the leading cell reprogramming company right now we've been able to to raise more than 200 million dollars so far and the objective is to create cells that we can use to democratize science give these to scientists but in particular to also create a new set of affordable cell therapies we are incredibly privileged to work with some of the leading innovators and this includes the chair of our board hermann hauser he's been at the center of two new industries he's one of the co-founders of arm so chip industry but it also sparked the sequencing industry by backing the technology that now most people are using and i've already told you about sir greg winter and maris vernick i'm also extremely privileged to work with roger peterson who is one of the forefathers and founders of human stem cell research and the cambridge stem cell institute so with a consistent and scalable source of human cells we can change the way that the drugs are developed let's think about alzheimer's we've not been very good at creating alzheimer drugs and one of the main reasons is because there's a difference between the animals that are used for research and the human beings that suffer from alzheimer's in fact there is not a single mouse on this planet that suffers from alzheimer's this is a entirely human condition so in order to create alzheimer's drugs scientists engineer the mice so that they get something that looks like alzheimer's and then companies run a very efficient drug discovery process and at the end of that when the drug enters in the clinic we learn that it doesn't work in fact we learn that probably what's been created in the mouse isn't quite what we need to treat so the way to fix this is to use human cells the cells that are actually affected by the condition but what i'm most excited about are cell therapies this is the first child that has been treated by a cell therapy this therapy uses blood cells immune cells from the patient and engineers them in order for it to recognize cancer so she's been cured from a blood cancer this is a very complicated process at the moment it's extremely expensive one treatment costs hundreds thousands of pounds imagine we can use this software approach to create cells at scale and make cell therapies affordable this therapy was based on t cells they're not very good at going to solid tumors they're rejected there's another immune cell type that is much better suited to that called macrophages so here you can see macrophages that have been programmed with our technology and they are fighting bacteria as they eat them they turn red this is just the beginning think about combining cells in order to print organs and organites or using nerve cells and integrate them into bionic devices to control artificial limbs moving beyond medicine the second company uses the technology to create cells for the manufacture of meat this will not only allow us to fine-tune our stakes but it also will tackle some of the challenges associated with farming like the use of antibiotics causing bacteria to become resistant or the greenhouse gases that are associated with farming and the risk that another virus transfers from animals to human beings causing another pandemic but this approach might take us beyond our planet because i don't think it's feasible to take a cow up to the station that we're going to build on mars finally we may be able to use this technology to create new kinds of computers here you see a living computer chip made of brain cells that are learning to play pong so when software determines the hardware anything seems possible thank you you | ↗ |
| 19 | Black Stone Physical Medicine | Latest & Greatest Advances In Regenerative Medicine | 342 | 10 | 2 | 71.9 | positive | 4:35 | Today we're going to talk about the top new advances in regenerative medicine. My name is Mark Musa and I'm an interventional pain physician. This last weekend there was a conference out in Florida, this Toby conference. It's a regenerative medicine conference. We have people come from all over the world sharing their research to do with regenerative medicine. This Toby conference in my opinion is probably one of the best in the nation. They have it every year. There's a couple other really good regenerative medicine conferences like the go-to-to but this is one of my preferred ones. So we flew out to Florida this weekend for the conference. Many of the things discussed the conference were not new. As new things are seen in regenerative medicine we kind of continue talking about them subsequent conferences. But there are two new regenerative medicine procedures that I want to discuss. The first one was the inner osseus regenerative treatments. So I've seen this coming around the last few years as we go to these conferences. Inner osseus is essentially where you take something and you inject it into the bone. This has been used for years by paramedics. If they need to give IV access and they can't get into vein they'll put it right in the bone and they can put you can put IV fluids into the bone. So over the years as we've looked at osteoarthritis first we would inject things into the joint like platelet-rich plasma or bone marrow concentrate some stem cells from the bone marrow. And then with a little bit more time we saw people treating the ligaments in addition to the joint itself and we saw better improvement. We know from physiology that the pain from an arthritic joint comes from the joint capsule as well as the bone. We call this sub-control bone so the layer kind of underneath the cartilage. And we've seen that if the arthritis gets severe enough there are some changes in the bone marrow. We call it bone marrow dima, essentially bone bruises. And there's been over the last handful of years more docs looking at this doing studies where they have been treating these bone marrow lesions. So I was initially skeptical so I've been watching to see what kind of results we saw over the years and it really keeps getting better and better. In this year they dedicated almost seem like a quarter of the conference to interosseous treatments. So what they do is they essentially stick a needle into the bone either through a crack or they drill into the bone and inject either play the rich plasma or a bone marrow concentrate right into the bone marrow lesion. And these studies showed pretty significant improvement in the patient's pain and function. So pretty dramatic improvement. And I imagine as we go forward this will be become part of a routine regenerative medicine option in addition to intradicular or directly injecting into the joint. The other new regenerative medicine technique that I want to talk about was something that I've been keeping my eye on for years. Nerve pain or neuropathy is always a challenge to treat an impain management. Not a lot of great treatments like for example peripheral neuropathy. Not a lot of great treatment options for that. Years ago there was an animal study that we saw where they injected directly into the nerve of an animal with this nerve lesion or nerve injury. Some play the response and we're right into the nerve and I thought that was pretty wild because we try to avoid injecting the nerve at all costs. So there's one presenter, one researcher at this last conference that studied actually that in humans which is the first time I think I've seen it in humans where they he would inject directly into the nerve with play the rich plasma and saw some significant recovery in nerve pain. So over the years we've seen most commonly done was something called hydro dissection where you inject around the nerve and separate it with the fluid you inject from the surrounding tissue. So many we've seen improvement with that. Often we'd use play the rich plasma for that as well or maybe something like a steroid or dextrous solution. And so this is taking that to the next level. You know I would imagine they'd do this if they had saw actual nerve fiber damage which you can see on an EMG. Interesting studies with that. I don't think I have a point where I would want to try injecting into the nerve quite yet. I'd want to see give this a bit more time, a couple more years and see what continues to show up with the research before I feel confident in doing this on a patient. And it'd have to be a pretty carefully selected patient with a specific type of nerve injury like a crush injury or something along those lines where we could easily do that. So it's really exciting to see these advances in and pain management really getting people feeling better so they can get back to doing what they want to do. Make sure to subscribe. Until next time. | ↗ |
| 20 | Sciencerely | How To Make Stem Cells | Yamanaka Factors | 215657 | 6804 | 297 | 70.7 | positive | 9:32 | Hey there, before we start this video I want to thank you for all your feedback in the last weeks. Unfortunately I was not able to use my microphone and therefore I had to wait until it could record this video. But you are here, I am here and this episode is going to be awesome, so let's start. Being the son of a small factory owner in Osaka, Shinya Yamanaka was born in 1962. As a child, Yamanaka was fascinated by the smanning clocks and radios into small pieces and trying to assemble him again. He was inspired by his father to become an engineer, however as a teenager he considered studying basic sciences and then finally decided to go to medical school. He became a surgeon but felt that his skills were not as good as expected. Furthermore he also realized that many diseases cannot be cured for surgery. So Yamanaka decided to immerse himself in the basic science and stat and was introduced into the fields of STEM biology. And after some years of research his passion led to the identification of the so-called Yamanaka factors. The Yamanaka factors are one of the most important discoveries in the field of STEM science research. Through the activation of Yamanaka factors we can produce for example STEM cells from skin cells. This means that we do not necessarily need to sacrifice embryos to conduct STEM science research but we can make them ourselves. And this finding resulted in Yamanaka winning the Nobel Prize in Physiology of Medicine in 2012. Okay but what exactly are the STEM cells and Yamanaka factors? My name is Gönstaniak and today we talk about how we can generate STEM cells from our own skin. As some of you might remember we previously talked about STEM cells in this episode here. However I think we should go into more detail in order to really understand STEM cells and grasp how we can generate them. STEM cells are a special types of cells which are able to serve in you and have the capacity to produce differentiated cells. To be more precise STEM cells can generate daughter cells which are identical to the mother or which have restricted potential. Potentially is defined as the number of possible fades as cells can acquire meaning that it can change over time and become a neuron or muscle cell for example. The more restricted the potential for cell is the less fades it can acquire meaning that it might become a neuron but not a muscle cell anymore. We call the process in which a cell becomes more restricted differentiation. Generally speaking we can distinguish between embryonic and adult STEM cells. Of course we only find embryonic STEM cells very early in development. Embryonic STEM cells can become a lot of different cell types and therefore we call them pluripotent. Adult STEM cells on the other hand are found throughout life and they are generally more restricted than embryonic STEM cells. We call them multi potent if they give rise to several cell types and unipotent if they produce the same cell types over and over again. Hematopoietic STEM cells are found in bone marrow and they are a great example for multipotent STEM cells as they give rise to all different components of the blood. On the other hand we also find unipotent STEM cells in our liver and they are the reason why our liver is able to recover after long night out. By now you might have realized that the potency of STEM cells generally seemed to decrease with development. While during early development STEM cells might become all kind of different cell types such as skin cells, neurons or muscle cells. Adult STEM cells are generally more restricted and might give rise to different components of the blood for example. This restriction however is very important as STEM cells might otherwise form what we call teratomas in our body. Teratomas are cancer like structures which could rise to all kind of weird different tissues. And teratomas might find teeth or hair where we don't expect them and to keep your appetite I will not include a picture of teratomas in this video. Oh man, I love this topic. So let's go on, we've discussed the two major characteristics of STEM cells. But here are some interesting thoughts. Embronic and adult STEM cells have the same genetic information as most other cell types in our body. So why do only STEM cells divide and give rise to these different cell types? And more importantly, can we also force differentiated cells to become STEM cells? We could actually spend hours trying to answer these questions and we also must realize that only a small fraction of STEM cell biology is understood. But very broadly speaking, STEM cells activate unique genes which are not activated in differentiated cells of our body. A lot of these genes produce so-called transcription factors, transcription factors are proteins which on the other hand activate many other genes downstream. In this way we can control the activation of many genes through only some transcription factors. Of course there are many other ways to influence STEM cells but we will not go into much further detail. But the important point is that some genes are only active in STEM cells and they are also required from maintaining their characteristics. So what happens if we also activate these genes in other body cells? Well, this question was answered by Shinya Yamanaka when he discovered and activated the soul of Yamanaka factors in fibroblasts which are found in the skin. And just to clarify, Yamanaka factors are four genes named Octophy4, Sox2, KLF4 and Cymic. These genes all influence the activation and inactivation of other genes. The amazing fact about Yamanaka factors is that they are not only very important for STEM cells but can also be used to generate STEM cells from differentiated cells. This means that we can reprogram cells to become STEM cells and in this regard we call an induced pre-reported STEM cells or IPS cells. And it was the identification of Yamanaka factors and the generation of IPS cells for which Yamanaka got a Nobel Prize in Physiology or Medicine. At this point it also makes sense to take a closer look on what kind of experiments Yamanaka conducted. In the beginning of the century his goal was to identify which genes are important for maintaining pre-repotency. And so he and other scientists started to identify genes which are highly active in STEM cells. But then in 2006 he wanted to see if some of these genes are not only important for maintaining pre-repotency but can also convert fibroblasts into STEM cells. And therefore he started to read a lot and he identified 24 candidate genes which might be important in his context. He then started to genetically change fibroblasts to become resistant against a certain drug if they are STEM cells. This means that these cells will only survive the exposure to the drug if they become STEM cells. He then fused the 24 candidate genes with parts of viruses in order to infect the cells. As a consequence they introduced genes become activated and Yamanaka saw that indeed after a while fibroblasts became STEM cells. But it didn't stop here since he thought that not all 24 candidate genes are equally important to make STEM cells. He then infected fibroblasts with different combinations of these genes. And this is how he discovered the Yamanaka factors. If anyone of you wants to become a researcher or is interested in STEM cell biology I provided you the link of the original publication in the description. I think it's a very great publication. Okay so we can now isolate fibroblasts from our skin and convert them into induced brew-putting STEM cells. But why is this important? The numerous different positive applications of induced brew-putting STEM cells. We can use them for example to generate tissues or organs. And this is a very important topic. In Germany for example the number of postmortem organ transplantations has declined by over 30% in the last 10 years. Induced brew-putting STEM cells have the potential to generate tissues or organs for transplantation. I also want to point out that these tissues or organs could be very compatible with the recipient if they derive from the patient's own cells. If you're interested in current advances in generating tissues or organs let me know in the comment section and we make another video about this. Induced brew-putting STEM cells have great potentials in clinical applications. However they also have one major drawback, the risk of developing cancer. You see, STEM cells and cancer cells show many similarities as they are both able to undergo extensive proliferation. Moreover many of the genes which are active in STEM cells are also active in cancer cells. For example one of the Yamannaka factors, CIMic is a proto-oncocene. This means that CIMic can provoke cancer if it is highly active in a cell. In the case of CIMic researchers have adapted Yamannaka's protocol in order to make this dangerous gene redundant. In Yamannaka's original publication the candidate genes were introduced into the cell by using viral components. Since these viral components can integrate into the genome that can cause damage or provoke cancer. Therefore we still look for the best alternative way we can use for example RNAs which do not integrate into the genome. But nevertheless in 2014 the first clinical trial using IPS cells was launched. Here in these probed in STEM cells were generated from a patient who suffered from macular degeneration which is the main cause of vision loss. These IPS cells were then transformed into a retinal pigment epiphylose cells which were then transplanted into both eyes of the patient. And the therapy was actually quite successful, the degeneration of the patient stopped and the vision improved. And so clinical trials in other fields such as heart disease that beat this Hispanic cord injury are in progress. If you are interested in these similar topics let me know in the comments section and leave a like. And don't forget to subscribe and hit the bell button in order to stay informed about the greatest discoveries in life sciences. And with that I'll see ya. | ↗ |
| 21 | Jeffrey Peng MD | PRP Injection vs Stem Cell Therapy for Knee Arthritis | 194481 | 4597 | 498 | 70.6 | neutral | 9:12 | So you have really bad pain in your knees and you've tried everything to treat them, but nothing is getting you relief. You've heard of a lot of success stories with regenerative medicine treatments such as PRP injections and stem cell therapy, but you're wondering are these stories too good to be true? Do people really feel better and who can you trust to learn more about these treatments? Well, you're in the right place because we're going to go through the most up-to-date clinical trial data. And these studies will tell us whether PRP injections and stem cell therapy actually work. They will hopefully help you decide which treatments may or may not be worth pursuing. Let's get started. Hey everyone, Dr. Jeff Payne here. Now if this is the first time you are watching one of my videos, my goal is to help each and every one of you live an active and healthy lifestyle. So if that's something you're interested in, please consider subscribing to my channel. Okay, so let's talk about PRP versus stem cell therapy for knee arthritis. Both PRP and stem cells fall under the big umbrella category of treatments called regenerative medicine or orthobiologics. These are very new techniques with the goal of using your own body cells to help relieve pain and inflammation. Both PRP and stem cells contain an enormous amount of growth factors. They initiate cascades, which are responsible for tissue healing, tissue remodeling, tissue proliferation, and in controlling pain and inflammation. But more specific to osteoarthritis, they are incredibly important in altering the biochemistry of a knee suffering from arthritis. And that's because arthritis causes a very toxic environment in the knee. It's incredibly inflammatory and all of this leads to pain and disability. So the goal of biologic treatments such as PRP and stem cells is to use your own cells to reset the environment in the knee to create and maintain a healthy and neutral environment. Our hypothesis is that these cells will not only reduce symptoms, but they can also decrease the progression of arthritis. So let's talk about stem cells first. What are they? When most people talk about stem cells, they are thinking of pluripotent stem cells. These are cells that can divide and grow into pretty much anything. Think of embryos that are just starting to grow and create new organs. They are incredibly versatile and can potentially regenerate or repair disease tissues in organs. But when we talk about stem cell procedures or stem cell injections, we are actually using and referring to another type of stem cell, not the pluripotent stem cells. Instead, we are using a special type of adult stem cell called the mizenchymal stem cell. These cells have limited capacity when compared to pluripotent stem cells, but they still have tremendous ability to reduce pain and symptoms. So the two most common places to get mizenchymal stem cells are either from adipose or fat tissue or from the bone marrow. And it's important to point out that once we isolate the mizenchymal stem cells and then inject them, there's no current evidence to suggest that we are re-growing or regenerating anything. Remember, these cells are not pluripotent. You don't get a new knee after stem cell injections. So you may ask, what's the point then? Well, mizenchymal stem cells are incredibly strong signaling cells. They initiate cascades in the body that provide all sorts of health benefits, but most important among them are reducing pain and reducing inflammation. And how does that compare to what PRP does? PRP stands for platelet-rich plasma. In PRP, we draw your blood into a specialized tube, put it in a centrifuge, and then separate out your platelets in all the growth factors that circulate in your blood. We then take that out and then eject it into your knees. Again, we are not growing or regenerating anything, but we are using the cells that initiate incredibly strong cascades in the body to provide pain relief and reduce inflammation. Our current understanding of mizenchymal stem cell injections and PRP injections is that they initiate similar pathways to help improve symptoms. The question then becomes, do they work? In which one is better? Let's tackle the first question. Do they work in treating knee arthritis? So this study looked at people with knee arthritis who were treated with adipose derived mizenchymal stem cells, so adult stem cells from fat tissue, and published their results at two years follow-up. In terms of pain, the researchers found that there were significant improvements at six months. At 12 months, pain was slightly worse than six months, but still better than before treatment was started. At 24 months, pain was essentially back to the pre-treatment baseline. In terms of function, the researchers found gradual improvements at six months, 12 months, and then a plateau effect at 24 months. These results included people with wild, moderate, and severe arthritis. Now I think it's important to point this out because our current medical thinking is that once you reach grade four or bonon bonarthritis, there's almost nothing we can do except for a new replacement surgery. In this study, people with severe arthritis definitely had improvements from their baseline, just not as much as those with mild arthritis. So what about mizenchymal stem cells obtained from bon marrow and how do they compare to the ones from adipose tissue? So this study was a systematic review and meta-analysis looking at 19 studies, and compared those who got mizenchymal stem cell injections from bon marrow and from adipose tissue. They found that both groups had significant improvements in pain and function for the treatment of knee arthritis. More interestingly, they found that the patients who got bon marrow mizenchymal stem cell injections had significantly better outcomes compared to people who got adipose derived mizenchymal stem cells. So from these studies, we know both types of mizenchymal stem cell injections are effective at treating symptoms related to knee arthritis, and it seems that bon marrow may be better than adipose tissue. Now what about PRP? Playlist-rich plasma injections have also been shown to be incredibly effective at treating symptoms related to knee arthritis. I made an entire video discussing PRP injections, which I will link here, so please check that out if you are interested. But here is one of the most recent studies looking at the use of PRP injections to treat knee arthritis. It's a systematic review and meta-analysis looking at 40 different studies comparing PRP to hyoronic acid, corticosterates, and placebo injections. They found that at six months, PRP was as effective and in some studies more effective than other therapies regarding pain, function, and stiffness. So all of these studies add to the growing body of literature, which supports the use of orthobiologics to help treat and relieve symptoms related to arthritis. But which ones are better? So the next question we want to ask is, are there any studies that directly compare mesenchymal stem cell injections to PRP injections? And the answer is yes. This study was published very recently and is a two-year outcome study, comparing bon marrow mesenchymal stem cells to PRP treatment. Patients with knee arthritis were randomized to get either one bon marrow injection or one PRP injection. And they found that both groups had significant improvements in both pain and function at three months, six months, nine months, 12 months, 18 months, and 24 months. But what they found was there was no difference. There was no difference between PRP and bon marrow mesenchymal stem cell at any time point. The researchers go on to conclude that for the treatment of osteoarthritis, PRP and bone marrow concentrate performed similarly out to 24 months. Bon marrow was not superior to PRP. So from these studies we can conclude the following. Both stem cell injections and PRP injections work similarly well for the treatment of knee arthritis. Again, we think they work by treating and changing the biochemistry inside a knee with arthritis. The hypothesis was that stem cells would provide a greater effect than PRP. But at this point in time, that hypothesis has not been proven to be correct. Both PRP and stem cells are equally effective. But here's the thing. Let's talk about cost. Both of these treatments are not covered by insurance and they are cash pay. However, stem cell injections can cost thousands and even tens of thousands of dollars. PRP is significantly cheaper in the hundreds of dollars. And until clinical trials start to show otherwise, when we do a cost benefit analysis, PRP is the clear and easy winner. Hopefully that provided a good summary of PRP versus stem cell therapy for the treatment of knee arthritis. My channel has an entire playlist going over PRP and orthobiologics. So check that out if you are interested in more content. And lastly, everyone who has knee arthritis really should take a multimodal approach to treating their knees. So check out this video next where I go through all the treatment modalities that I recommend most. Thanks for watching. | ↗ |
| 22 | WGN News | Chicago scientists develop revolutionary cartilage regeneration techno... | 739462 | 14605 | 1768 | 70.4 | positive | 2:46 | On the Medical Watch for you this afternoon, a breakthrough in orthopedic research that could revolutionize joint care. A local lab has developed a treatment to potentially enhance damaged or naturally deteriorating cartilage. W. J.N. S. On the Medical Watch, it's the Holy Grail in orthopedics, finding a way to enhance damaged or naturally deteriorating cartilage. Now a local finding in the lab stands to revolutionize joint care, turning back the hands of time. We run them down. It doesn't regenerate easily at all after you are fully developed. It's all we get. Once the body is done growing at about age 18, so is our cartilage. And as we age, the thin layer of tissue that covers our joints wears down. And when it's damaged, then you have not only pain, but difficulty walking, moving around. That's why the quest to regenerate cartilage is a robust science. From surgery to stem cells, doctors are always searching for methods to mend the wear and tear we place on our joints. Cells by themselves is not a good strategy. I mean, you need a matrix, so to speak. So our material is a matrix. It took decades of work to fill these tiny vials. Our intent is to be able to use this material to regenerate defects in cartilage or damaged cartilage. What looks like a gel is actually a highly bioactive substance made up of peptides, proteins, and polysaccharides. The goo doesn't just fill a gap. In our case, our materials have signals in their structure to communicate the cells and get the cells to regenerate a specific tissue. In this case, cartilage. Dr. Stoop and his team tested their substance in sheep. Sheep, of course, is as large as we are and as heavy. And therefore, it's a very good preclinical model to predict what might happen in humans. What happened? The sheep grew cartilage. It removed healthy cartilage, then filled the defect with our material. And then six months later, and we see that authentic cartilage has been regenerated in the place where there was a defect. But it is clear that moving forward, there will be great interest in regenerative medicine. The next step is to test the substance in small defects, like those suffered in sports injuries or trauma, with the ultimate goal of helping patients avoid a total joint replacement. Back to you. | ↗ |
| 23 | Professor Dave Explains | Immunomodulators Part 1: Immunosuppressants | 45234 | 1120 | 49 | 69.2 | positive | 8:31 | E nos laudate la science da prefessa, David explains. In the previous tutorial, we discussed glucocorticoids, which interact with the immune system. Let's now generally discuss immunomodulating drugs that go some distance in establishing harmony during immune system dysregulation. Immuno-modulating drugs can be broadly separated into a dichotomy of immunostimulants and immunosuppressants. As these names suggest, immune stimulating drugs work to enhance specific functions of the immune system while immunosuppressants inhibit immune function. In this tutorial and the next, we will survey pharmacological mechanisms and try to understand how these two drug classes achieve immune system modulation. Let's start with immunosuppressants. The most clinically relevant and actively researched class of immunosuppressants are the glucocorticoids, which we discussed at length in the previous tutorial, so these will not be discussed further here. However, it is worth emphasizing that when it comes to immunosuppression, glucocorticoids are king. Even still, the other classes of immunosuppressive drugs are certainly important and sometimes used in conjunction with glucocorticoids, albeit in more specific and less common medical situations. These include reducing the risk of organ transplant rejection and stent stabilization in the case of blood vessel occlusion to name a few. There are four main classes of non-glucocorticoid immunosuppressants. These are immunophylline binding drugs, cytostatic drugs, anti-limphosite antibodies, and monoclonal antibodies. First, we will cover immunophylline binding drugs. Immunophyllines are cytosolic proteins that catalyze the biochemical reaction of cis-trans isomerization for the amino acid proline. This isomerization is critical for the correct folding for many proteins in achieving the right three-dimensional structure. These proteins have a wide range of isoforms and functions and are highly conserved in terms of evolution, existing in eukaryotic and prokaryotic cells alike, but in the context of immunosuppressants, immunophyllines act as the receptor for this class of immunosuppressants. Cyclosporin and tachyrelemus are examples of immunophylline binding drugs. First, after administration of the drug, it enters the cytosol of T cells. Here it binds with immunophylline and following drug immunophylline complex formation, the complex binds to another intracellular protein called calcinurin. In the absence of these drugs, calcinurin usually acts as a transcription factor to promote the production of interleukin 2. However, following immunophylline drug complex binding to calcinurin, the interleukin 2 transcription activity is inhibited. Since interleukin 2 is a proimmune chemokine that increases the activity, maturation, and differentiation of T cells, reduction in its production predictably leads to immunosuppression. Another similar immunophylline binding drug worth being aware of is rapamycin. In the context of immunosuppression, it also leads to the inhibition of interleukin 2 production, but it does so via inhibition of the mTOR signaling pathway, not from calcinurin inhibition. In fact, this is how the important mTOR signaling cascade was named, mechanistic target of rapamycin. These compounds are primarily used for immunosuppression after organ transplantation and in rare cases to treat some autoimmune diseases. The second class of drugs are cytostatic drugs, which means they inhibit cell division. The aim of these drugs is to reduce the proliferation of T and B lymphocytes. This is achieved by various mechanisms focusing on the rate reduction of cell division through the inhibition of DNA replication. In a previous tutorial, we discussed metatrexate. This is a commonly used cytostatic drug that achieves immunosuppression by inhibiting the enzyme dihydrofolate reductase. The consequence of this is inhibition of thymidine synthesis, a critical deoxy nucleoside for DNA synthesis and replication, hence reducing cell proliferation. Of course, many other cytostatic drug mechanisms will be elucidated more thoroughly when we discuss cancer chemotherapy. Since disrupting DNA replication and regulation are the main focus of many cancer chemotherapy drugs, which aim to reduce the rate of tumor growth and proliferation. With this in mind, it is intuitive to see the overlap between overactive immune responses caused by autoimmune diseases and cancers that increase proliferation of different white blood cells. To this end, many similar drugs with immunosuppressive qualities are used to treat both immune system-related cancers and autoimmune diseases. However, from a different perspective, an important concept of pharmacology is to appreciate that adverse effects in the treatment for a particular pathology may be therapeutic for a different pathological condition. In this instance, when treating cancers that don't increase immune system reactivity, cancer chemotherapy drugs often have the adverse effect of immunosuppression, but in cases of immune stimulating cancers, immunosuppressive qualities are therapeutic. This can be confusing, but the main aim of pharmacology is to establish equilibrium in pathological dysregulation. The last two categories of immunosuppressive drugs we will discuss are anti-limphysite antibodies and monoclonal antibodies. An example of an anti-limphysite antibody is the drug Alim Tuzimub. This drug binds to CD52, a glycoprotein on the surface of mature B&T lymphocytes. Once it binds to the glycoprotein antigen, it triggers cell apoptosis. It's intuitive to understand that by shifting the equilibrium toward increasing apoptosis of lymphocytic cells, an immunosuppressive effect is achieved, as dead immune cells are unable to carry out immune function. This drug is used for the autoimmune condition multiple sclerosis, a condition where the myelin sheath of neurons is destroyed by the immune system. But it is more commonly used in some leukemias for its anticellular prolific effects on B&T cells. Lastly, let's mention one immunosuppressive monoclonal antibody. Muromonab binds to the CD3 protein of the aptly named T cell receptor on T cells. When this antibody binds to CD3, apoptosis pathways of the T cell are triggered, leading to immunosuppression. These drugs are often used in acute organ transplant rejection that are glucocorticoid resistant, as well as some T cell related cancers, such as T cell acute lymphoblastic leukemia. So that covers an introduction to immunosuppressants. Let's now move forward and examine some drugs that have precisely the opposite effect. | ↗ |
| 24 | Protocol Labs | Brain Rejuvenation by Partial Cellular Reprogramming | Yuri Deigin | 1850 | 68 | 5 | 69.1 | positive | 58:59 | welcome everybody to this session my name is Yuri denan I'm the CEO of Youth Biotherapeutics and today I'd like to tell you about partial reprogramming and uh in particular its application to the brain which is what precisely we're doing at youth bio and uh um just a few words about who I am just so you know um I've been a drug developer for over 15 years and I've been a longevity activist for over a decade and uh I'm one of the earliest proponents of partial reprogramming as you can see on the slide I founded the first company dedicated to partial reprogramming in 2017 and uh to translate partial reprogramming into therapies unfortunately I was a bit too early investors thought I was kind of crazy trying to uh activate yamanaka factors in the brain uh but uh thankfully other people came into uh the area like people like David Sinclair and investors got much more comfortable and people like Jeff Bezos or us Miler poured like $3 billion into partial reprogramming companies and so in 2020 I started use bio where our Focus from the very beginning was on the brain and uh let me just uh say a few words about why I'm so bullish about partial reprogramming and then I'll dive deeper exactly what partial reprogramming is for those of you who don't know but the next few slides are just like a movie trailer preview of what's to come in my presentation and why par programming is so awesome and it's it's awesome because it has the potential to completely revolutionize medicine and if in 2017 I was one of the few to recognize this potential as I mentioned now there's a lot more people like Joe Bezos who've also recognized it and poured billions of dollars into it I mentioned Alo slabs which is probably the most most known example there's also Sam Alman who financed retr with like $180 million there's Brian Armstrong of coinbase he's financing a new limit with $100 million so partial reprogramming now is is really taking off and for good reason because reprogramming has been shown to rejuvenate cells fully rejuvenate cells on the cellular level and amarate homeworks of aging and so it's been demonstrated to be effective in many different cell types and different cell types have like different diseases associated with it so there's like dozens and dozens of diseases in which partial reprogramming can have potentially therapeutic benefit so collectively this has the potential to be like a trillion dollar field if these therapies are indeed proven to be effective and safe and go on the market and it all started with this paper this 2016 paper by ampo all out of the sulk Institute which demonstrated that parure e programming can extend lifespan by up to 50% in Pro mice these mice are fast aging mice but yet this is a very compelling result and it showed that Not only was their lifespan extended it also showed they had many any other benefits relative to home marks of Aging or relative to their his tissue histology basically it made tissues look younger or at least physiologically younger and also more importantly recently there is a result in normal mice uh completely normal mice not transgenic animals with a gene therapy approach who've been shown to extend lifespan bip partial reprogramming the previous model was a transgenic animal so it's it's really complicated to translate this into humans because we're are already kind of formed without the Amica factors so we need a gene therapy approach and this paper kind of recapitulated what we would expect from a therapeutic standpoint it had a gene therapy with OS delivered to these old mice and that extended their lifespan by not much but as a proof of concept showing that it's possible to use par programming to extend lifespan of normal animals and as I said this is a preview I'll go deeper into each of these things later on in the presentation uh but also besides extending lifespan partial reprogramming has been demonstrated to be effective in many different models of disease I mentioned theoretically it could be a trillion dollar market because by now I think there's been like a dozen studies in different disease models showing some sort of therapeutic benefits and this slide is about Alzheimer's which is very dear to my heart and this is what we're doing at youth bio showing that parure programming can have beneficial effects beneficial therapeutic effects in a mouse model of Alzheimer's and I was very happy to see this paper this is not by our group but we're also doing of course Alzheimer's research and this essentially validated the findings that we observed in our studies of our Gene Therapies in our Alzheimer's Mouse model so now that you're hopefully interested to hear more about partial reprogramming let me give it a proper introduction but for a proper introduction of course we need to talk about why is it that we need to rejuvenate things in the first place and of course this is because of Aging so we need to talk about aging but before we do let me just point out uh kind of an interesting Paradox that we've been discussing here in the past few days that when you ask people like the general public do they think we should be eradicating cancer and everybody's like yeah yeah we should cure cancer and you ask them what about Alzheimer's everybody yeah yeah we should cure Alzheimer's and if you ask them pretty much about any disease they all think yeah diseases need to be cured we should eradicate all diseases and then if you ask them okay let's imagine we've eradicated all disease and also figure out how to keep you young for as long as you want how long would you like to live in that scenario and people still say that oh maybe just 100 years and to me this is mindboggling like why do you want to have some sort of external externality determine how long you live shouldn't that be your choice shouldn't you live you know for as long as you want rather than have something externally determin that and it's funny that even within edes moral the mark Haman did a poll only about a quarter people attending this very Progressive you know Gathering of you know hopefully very smart people only about a quarter of those people say they would want to live in indefinitely and others still want some sort of like external uh expiration they put on them so um I I find that mindboggling because basically you know this ability this option to to determine ourselves the control of our biology including how long we want to live I think it's so valuable that we should all be you know trying to get it and support the research that is trying to um uh give this option to everybody in the world and I think the reason why people uh don't really they think they don't want it is just because collectively Humanity has this sort of Stockholm syndrome when it comes to aging and death and I think it's is a textbook case of learned helplessness and I think Aubrey deg gr put it really well he said that we all grew up with the idea that aging is inevitable and so we rationalize that okay if it's in inevitable even if it's really bad we can't do anything about it so let's just accept it and pretend that we didn't really want it in the first place like oh okay you know it's it's impossible so I don't even want to live for as long as I want but of course thankfully science and technology has been kind of pushing away from like pushing on death and aging for the past you know many many years including extending our lifespan for example in the past like 100 plus years we've extended the median lifespan from about 50ish to like 80ish so that's a 30-year increase in median lifespan and there is still room to grow because the oldest humans are known to live to about like 120 just a bit Les a bit less so there's still a lot of room to grow just within the known human lifespan between 80 and 120 and also this is just kind of known biology but of course there's this X Factor U that can potentially extend it much farther Beyond 120 that has to do with current you know research genetic engineering and the novel things that will eventually become modern medicine which they haven't yet but this is once they do this has the potential to extend our lifespan much greater because right now we finally we collectively as Humanity finally have the tools to modify our biology in you know ways we couldn't imagine maybe just a few decades ago so it's it's I think basically what I'm trying to say it's time to kind of get away from our learned helplessness and at least put ourselves much much more um Higher Goals of what we want to do with our health and our biology and of course the inspiration from to to the previous slide that we can extend our lifespan much more significantly stems from the observations that in nature there're animals who live much much longer than humans do by like 100 200 or even 300 years they live longer than us so with the proper tools that are disposable like genetic engineering we can potentially you know reach or even surpass those same lifespans because we know that even some mammals they live for over 200 years so I don't think it's you know out of the realm of possibility of figuring out the mechanism behind that and also implementing them within ourselves and besides mammals there's green shark that's known to live over 400 years some estimates even say over 500 years and so the problem that we're trying to solve at youth bio and the rest of the longevity field is the aging process itself we're just trying to do something about well about those kind of later years marked by bad health and suffering and initially would like to figure out how to slow down the aging process extend the healthy years of Our Lives then learning to stop a all together just to maybe even prevent ever having to suffer from the diseases of aging and ideally develop ways to reverse aging for those people who kind of have already entered the not so healthy years of Our Lives to bring them back into good health and allow them to um enjoy that good health indefinitely and so this is why we're called youth bio we want to extend not just Health span or lifespan we want to extend your youth span which is the most enjoyable and most happy and most healthy time of our lives and so one possible solution of how we can do this is cellular reprogramming because on the cellular level reprogramming has been shown to rejuvenate cells and accomplish pretty much all of the things that I was talking about on the previous slide including ameliorating all cellular homeworks of Aging that are listed on this diagram I have a pointer oh no I don't um but basically this diagram shows that the reprogramming process reverses all the homeworks of Aging that are known to occur at the cellular level and so now the biggest challenge for our field is to translate this these results from the cellular level to the organismal level and enjoy the benefits of Rejuvenation in our already adult organisms and just before we go go deeper into reprogramming just like let me briefly talk about what aging is and actually there's no consensus in the field on people scientists that study aging don't completely agree even on what it is of course there's Hallmarks of aging and I think we actually all of us know it when we see it like we can very well tell apart an old person from a young person but then having a precise definition scientific definition of course is a little more complex than that but you know obviously aging involves the worsening of our ability to maintain homeostasis and it's known to be associated with all sorts of Hallmarks listed on the slide and really the the biggest problem with aging is that it kills us and the fact that it it not only that the rate at which it kills us or the risk at which it kills us grows exponentially with age and so for like since about age 10 the risk of dying doubles every eight years and if for a 20-year older annual risk of death so risk of dying within one year is about 1,000 which is very low just imagine if we are able to freeze aging that such a person would be like mathematically expected to live a thousand years but then for a 60-year-old it's already one in 100 and for an 80-year-old the risk of dying within one year is one and 10 so you can see the exponential increase in that risk and before killing us of course aging makes us suffer with this arenol of unpleasant diseases all of which also increased exponentially with age of course the two biggest killers are heart disease and cancer I'm sure most of you know this and there are a few other Pleasant things like dementia which you know also not not a fun thing to have um and the second biggest problem with aging is that besides actually killing us it uh starts so early the process of Aging starts so early I think we barely get to enjoy our you know fully grown bodies until and they when they start falling apart at like age 40 basically and the pace of this falling apart is is infuriatingly quick so of course The Logical question then is why does aging happen at all and as I mentioned scientists can't even agree on what aging is so obviously there's no consensus of on why aging happens and some people like John and be may think that aging is completely random other people kind of on the end of the spectrum think aging is programmed me and there's I think then there's this Continuum between the two poles something that might be like an accidental program and obviously nobody's denying that there are some stochastic random changes with with aging the question is what plays a bigger role and what allows the stochastic events to eventually start accumulating as damage and why doesn't that happen for example in the first 20 years of Our Lives I won't get into like the debates on the uh what exactly causes aging we can just uh for now for just for the benefits of of this presentation look at empirical facts and kind of draw conclusions in terms of what things we can modulate and what things matter more and what things matter less look at just kind of the Animal Kingdom and inform our opinion on what we think are more important or less important aspects of aging and I think epigenetics is a more important aspect of Aging just kind of like a preview and the next few slides we'll try to make that point and of course this slide uh I think the main takeaway is that aging is just not Universal there's so much variation in lifespans and so like rates of Aging in the animal kingdom some species live just for a few days other species live for like a thousands of years and even within the mamalian kingdom among mammals the variation is like two orders of magnitude Mount lives 2 years whale 200 and so um but even within much closely related species than a mouse and a whale like for example this genus of rock fishes which are you know very similar evolutionarily related species on kind of their their philogyny they have huge variation in lifespan between like some some rock fishes live just 10 years and others live for over 200 years and it's not just two species it's a continue of 50 different species with kind of very smooth increase from like 12 years to 205 years between them so again aging within like I think on the power of evolution to really adapt to particular eological Niche aging can be varied very you know easily at least on an evolutionary time scale and I already made it the point that aging is not Universal but this slide tries to show just how variable the patterns are in the animal kingdom and to me this means that there's no single fundamental like physical law like say some people say oh it's the second law of Thermodynamics entropy has to increase but actually when it comes to the Aging of biological systems that's obviously not why we age and of course being open systems we can take in energy and matter and decrease entropy and so there has to be a aging has to be a biological phenomenon rather than just a phenomenon of physics and clearly aging is under genetic control uh because you know DNA determines how long a species lives and of course there's some variation between individuals there could be also some inputs uh based on environment but all of this happens within the confines of the life history encoded by genomes and um this is I mean we understand this from a basic level that's everything encoded in the DNA that then drives the morpholog morphology and the subsequent life history of a given species and the good news that genetically prolonging lifespan might not require massive genetic manipulation as kind of two quick examples show here in in mice just a single Gene actual knockout or knockdown can greatly extend lifespan and by almost like 70% and in nematodes a single Gene knockout increased the lifespan by 10 times so obviously with simple genetic manipulations it's possible that we can greatly uh increase lifespans and also artificial selection can ex uh greatly extend lifespan as well this is a famous Michael Rose experiment in fruit flies which initially increased lifespan in those flies by like 30% they continued running this experiment for like many many years years and ultimately they claim to have extended lifespan of these fruit flies with just like you know random mutation but artificial selection by up to seven times which shows that on a very very small evolutionary time scales like our time scales you can greatly increase lifespan and so to me this shows that there's a lot of potential for lifespan increase with genetic and I'll make the case later epigenetic modulation and so uh the next few observations are devoted to this hypothesis that it's also epigenetic modulation that can greatly vary lifespan on a level of a single individual and of course this has important implications for us because I think we all want to also be able to extend our lifespan rather than kind of live with a happy thought that eventually Evolution might extend human lifespan sometime in the future I think we actually want to get to live to see that they are s and so the next few observations that kind summarized on this slide I'll just quickly go into some detail about them why I think there's a strong case that there's epigenetic control of Aging as well and just briefly for those of you who might have not heard what epigenetics is this slide tries to summarize it basically epigenetics is control of gene expression so we are a multicellular organism we have 200 different cell types but of course each cell has the identical copy of DNA and so for each different cell type we the cell needs to have a certain set of genes on and off and so the mechanisms that control this are called epigenetic mechanisms and there's various different mechanisms I won't get into like exactly each once basically we need we need this system of control of gene expression and this is what we call epigenetics and also within aging we observe that these epigenetic changes happen during our aging with some genes kind of going down in the volume there's also it's not just the binary on or off there's also like a volume knob and some genes get silenced other genes get upregulated and these mechanisms are uh being observed to be play an important role in aging and let me just now share a few more observations from nature that I think show that aging could be under epigenetic control and of course the most clear example of this is social animals where you have identical DNA in the same kind of uh twins essentially determining very different lifespan if uh this individual ends up being a queen it lives by you know several times or sometimes in order of magnet longer than the same individuals with the same DNA but who went to the worker path and an even more extreme disparity is observed in ants their ant Queen lives for like up to 30 years and worker ants live like just one or two years and yeah like when I first found found out about examples my eyes were like enlarged just like yours I'm like holy as a small insect that lives longer than a horse or like twice as long as a dog this is like incredible that's probably longer than most Maman species 30 years and U yeah this I like wow uh I really like this example because previous examples of course they were based on like the social role of the insect and some people argue that essentially like two different programs in the same DNA that just like at Birth you go One path or another that determines your lifespan but in this case this shows that epigenetics can influence the lifespan even in the context of a single individual and it can actually be reprogrammed uh epigenetically and have a much longer lifespan in this case if this an it it's born as a worker but then under some uh circumstances in the colony if if the queen dies workers can become breeders and in that case their lifespan is significantly extended and so this to me shows again the power of epigenetics to modulate and change the fate and lifespan of an already formed individual and here's an example another example of extreme variation in lifespan brought about by epigenetics and I like it even more because mon butterflies they do not have different social roles and the only thing that determines how long they will live is the season in which they're born if they're born in the summer they live very short like about a month but if they're born in the fall then they need to migrate down to Mexico for the winter and basically in that case they live for like nine months and so this is again an example how epigenetics can greatly modulate lifespan of the species and we even observed this in some mammals because there's this rodent in Montana that have a similar pattern that if they're born in the spring then they sexually mature within the same year they breed and they die by the end of the year but if they're born in the fall then their development is put on pause and they actually sexually mature after the winter and so this also greatly extends their lifespan and the previous examples they were like about insects or animals of course we're much more interested in ourselves humans and while we don't have as clear examples of epigenetics playing a role in our aging but now we have Le circumstantial evidence that there is also epigenetic control of our lifespan thanks to these epigenetic clocks that have been discovered about a decade ago or even more than a decade ago by now and they show that uh there is this clock that ticks in our cells even sometimes very different cells this slide shows different tissues which show that this clock is synchronized between cells as different as a neuron and a blood cell and yet they show the same epigenetic time and so if you take a cell from an individual you can actually tell how old that individual is without knowing anything about them uh and so this shows that there is a some sort of epigenetic process some people like myself argue epigenetic program running that with aging modulates the epigenetics of very very different cells and another observation about these epigenetic clocks that they actually take slower in animals that undergo known interventions no interventions known to extend lifespan or slow down aging so basically they show that these clocks are kind of causitive and not just correlative so if you use an intervention to slow down aging basically this will be reflected in the clocks and if if you weren't yet convinced that epigenetics plays a key role in aging I hope the maybe next few slides will maybe convince you because uh these ones present uh the latest discovery that not only do all mammals have these epigenetic clocks this is worked by Steve horv and and his colleagues but you can actually build a panaman epigenetic clock that has the same underlying sites in the genome so basically it's like a a conserved epigenetic clock that reuses the same sites in the genome between very different species and the only difference between those clocks is of course the speed with which they tick so they use the same sides in the genome and the only difference is the speed with which those sides in the genome change over age so basically you could say that a mouse epigenetic clock just based on built on this cpgs just uh is ticking 30 times quicker than a human it's still the same same kind of epigenetic program it just ticks faster and I think this is a compelling evidence that there's some underlying epigenic program running with aging and so also these clocks have been shown to be very accurate across pretty much all mammals regardless if they're shortlived or long lived and to me also another convincing observation is that the clocks they were built based on adult tissues and yet when they observe the epigenetic timing in uh tissues from like embryos or development developing um uh individuals they show that the clocks recapitulate the development process even embryogenesis but the only difference being that that process is exponentially faster so basically uh and we also see this kind of remarkable conservation among species essentially we see that pretty much in all mammals the first 10% of our life history is spent on development according to these epigenic clocks which moves at an exponential ually quicker Pace than the the rest the other 90% of our life history and so this I think is this kind of ultimate evidence of a conserved eptic program running with at least the Maman genomes that determines the Aging life history or the Aging trajectory of our species and so the B the the basic kind of variable in this program is just the speed at which the clock ticks so like mentioned the mouse clock just moves 30% uh 30 times quicker than a human clock okay enough with like theoretical epigenetic uh questions the I think the question that we're all kind of wondering about is if aging is under epigenetic control can we actually do something about it can we reverse it of course epigenetics is reversible so it's U The Logical inference to make is that can we actually use epigenic to reverse aging and obviously in nature we see Rejuvenation happen all the time and uh it just seems to be reserved for reproduction in fact I think it's a requirement for reproduction without Rejuvenation post reproduction we wouldn't be here as I think there would be some sort of accumulation of of damage from one generation to the next but thankfully after fertilization the damage gets cleared and we have evidence of this from many different species showing that there is active clearance of damage there's active Rejuvenation that is tied to reproduction Even in our organisms as simple as yeast which are just you know unicellular single cellular organism which like a special case they can reproduce both sexually and asexually they can just do cloning and if they do cloning asexual reproduction they age but as soon as they're forced to reproduce sexually through like gametogenesis process they are rejuvenated and so this observation seems to be uh very again evolutionarily conserved about this rejuvenation to reproduction and it's been observed you know also to be the case in mice that also clear damage after fertilization in nematode worms by this was shown by Sy Kenyon team they have the same process of damage clearance in sexual reproduction in frogs also similar observation there's active Rejuvenation happening after fertilization and and a very interesting observation kind of Shifting Gears again to epigenetics is that what actually happens when people what happens after fertilization when people look at epigene clock is that the Rejuvenation event is not immediate it doesn't happen right after fertilization but it actually reaches a minimum at about day 10 if we talking mice which is coincides with gastrulation and so this implies that there is some sort of active rejuvenating program tied to reproduction that actually takes some time to work its magic and rejuven cells and uh this was a paper by the gladish group this is another paper by the gladish group but by Alex strap that also confirmed the same findings but at a single cell resolution basically showing that there's an active rejuvenating program happening after fertilization which reaches the minimum during gastr relation and another paper from the same group but looking at frogs showing that in frogs also the epigenetic epigenetic age reaches a minimum at gastrulation okay now let's talk about reprogramming with like this whole Preamble of what actually happens during during aging from epigenetic standpoint now we can talk about what we can do about it and how we can modulate epigenetics and just historically uh I think we should start with the Dogma that was prevalent in like the 19 or at least formulated in 1940s and was prevalent until uh very recently that uh cell differentiation is a one-way process basically everything starts as an embryo and then cells roll down this landscape and differentiate into eventually like a neuron or a skin cell but they can never come back up that was the Dogma that was called the wton landscape formulated by Conor wton and everything pointed that there's some sort of like irreversibility to this process however very quickly just 20 years later that Dogma was uh at least the first time proven wrong by John giren who showed you can actually take a nucleus from a skin cell put it into u a an egg cell we're talking frogs here and you can generate a whole complete organism and this refuted the the notion that the skin cell somehow loses the DNA that necessary to form other cell types and so this was kind of the first instance of uh at least showing some doubt in the Wasington dogma and it was again repeated in the 1960 1990s 96 which famous Dolly the sheep cloning experiment which is essentially a repeat of the John giren experiment from like 30 years before but it again showed that actually you know there there is some potential for reversibility and the this was conclusively proven in 2006 by sh yaka that not only showed that it's possible he showed how to do it he showed that if you induce these four factors transcription factors that are later came to be known yaka factors then you can take any cell all the way back to this embryonic ground state and so after this discovery for which he got a Nobel Prize in 2012 and of course Jord Gorden also got a Nobel Prize they shared the Nobel Prize they updated epic lens came became essentially bidirectional it showed that you can move up and down and actually you can move across you can take a skin cell and trans differentiated it into a neuron without actually needing to go to the ground state and with that finally uh after this discovery we have entered the possibility of how to affect this epigenetic Rejuvenation that I've been kind of hinting or talking about in the previous few slides and the observation that really set people in motion trying to accomplish it was that during reprogramming the cells are not only epigenetically rejuvenated they don't only go to the ground state based on like development or differentiation they're also physiologically rejuvenated like I mentioned the Hallmarks of Aging in in the first few slides and the first observation came from Jean maret team and inserm that you can take uh like cells from very old people you reprogram them into embrionic plottin stem cells and then you reprogram them back into fiber blasts and those fiber blasts are fully rejuvenated it's as if they were from very young people and so this uh then got researchers looking at other homeworks of Aging repeating the these experiment or doing new experiments and this is what then formed the basis of this diagram essentially summarizing many different uh um papers and a lot of research showing that all cellular Hallmarks are ameliorated by the reprogramming process and the next logical question for the field of longevity was of course can we capture this rejuvenating effects of reprogramming and use it in V use it for rejuvenating adult organisms and the the first attempt at this wasn't really successful it the but the first ever group to try this was monal sanos group from Spain in 2013 what they did is they basically created a transgenic Mouse model in which these yanaka factors were in every cell but they were silent until you actually induced them and then they tried inducing them in adult mice and they didn't really see a positive effect basically they saw that those mice died like weeks after they started the induction of the of the yaka factors and so the title of their paper wasn't very reassuring it was like uh reprogramming in Vivo produces teratomas and ipf cells with 30 potency features teromas are of course like tumors and uh I I don't think anybody reading that paper's even title would be you know very inspired to start doing par reprogram uh but thankfully Alejandra campus group was not deterred and and they actually figured out how to use partial reprogramming in Vivo safely to get just the positive effects without the negative effects and the genius of ampo and his colleagues were that you have to do reprogramming for very short durations and that's what came to be known as partial reprogramming because if you allow reprogramming to proceed too far you get side effects that eventually kill the mice which is what you don't want but if you induce yanaka factors for just like a couple of days you get red rejuvenating effects and that what led to this liman extension by up to 50% if you compare it to the first control group or 30% if you compare it to the third control group but basically that was the therapeutic result that they observed and even visually like people who work with mice can can tell a difference that like the control group has the sky phosis this curvature of the spine that is anaging hmark whereas the treated Mouse does not but more importantly not just from appearance but like on the biomar level the level of tissues the mice that were treated by yanaka factors were younger according to these metrics they had fewer cin cells fewer DNA breaks uh their tissue hystology was better like there's four different tissues listed here skin spleen kidney stomach Etc and uh oh they had yeah even better hair and hair of course is a hair thinning and hair graying is a homework of Aging um and so this kind of summarizes why I am so bullish about partial reprograming basically because I think it works at precisely the level at which our biology happens it works on the cellular level and regardless of you know the Matrix and the uh things that happen around the cells ultimately all the signals have to be processed by the cell and the the cell really decides how old it is right if the Matrix tells the cell you're old if we intervene at the level of gene expression and say don't listen to The Matrix you're still young we upregulate the genes that you know are associated with the younger cell then really we can circumvent the external signaling not to say that I don't support other approaches like replacement I think there's a lot of potential Synergy and replacement is also a completely viable option but I think also think paral reprogram has a lot of potential because we can actually by changing the gene expression of the cell which what what par does we can circumvent uh the aging process and so I guess one of the next interesting question is how does par reprogram work what you know where does the magic come from and unfortunately the exact mechanisms are still unknown I mean we know how reprogramming works and again from like a very mechanistic standpoint that it opens up chromatin silences one set of genes regulates or starts expressing another set of genes and ultimately this leads the cell to this path to PL potency where it it starts expressing the genes associated with ploty but where exactly in that process the rejuvenating aspects happen we still don't know but uh let me just kind of share some of my some observations that and speculate on what I think might be happening that uh could explain the rejuvenating aspects of par reain and I guess the the first question is so what exactly do yamanaka factors do and I think a lot of people already know that yamanaka factors are the factors that are responsible for maintaining stemness in these embryonic stem cells but and they're also known to be these Pioneer transcription factors that are able to access closed chromatin and start opening it up but I think what's less known about yaka factors that they're also the factors that trigger this maternal to zygotic transition during renesis and I'm getting maybe a little bit deep into like embryology but this is the process where the maternal genome gets silenced in just a few days after fertilization and the Genome of the you know ultimate resulting organism starts being activated and so if you remember the yeah that starts in the blast stage and and basically continues in the gastrol estage and if you remember this paper from the gladish group that shows that embryonic age embryonic igen age reaches a minimum at this blastula stage uh I think Gast stage again I think there's a lot of um good reason to believe that there might be some overlap between the rejuvenating program that is normally activated during embryogenesis and basically what transcription factors IM Manaka factors also trigger in the early stages of the reprogramming process so basically maybe the same gene networks that are responsible for this Rejuvenation that we see during embryogenesis are being activated by the reprogramming process and um yeah and this I think this gives a new meaning to this fun quote about gastation that it's not birth marriage or death but gastrulation that is the most important time in your life because that's what rejuvenates you as an organism okay now just still in the question of how does partial reprograming work but Switching gears from like the hypothetical scenario to just the empirical observation we don't know it maybe exact mechanisms but we do know that partial reprogramming leads to Rejuvenation so in particular the we can see this Rejuvenation on the transcriptomic levels the levels of transcripts mRNA produced by by the cell we see that uh after partial reprogramming the pattern the gene expression pattern the transcriptomic pattern of the cell is shifted towards the pattern observed in younger cells of the cell of the same cell type and so this is one result showing this here's another study showing the same observation that you're rejuvenating cell at the transcriptomic level the level of mRNA and of course I previously showed that par program rejuvenates cells at the epigenetic level the level of epigenetic clocks and so also on the third level just a level of physiology there are also observations that partial reprogramming induces this physiological Rejuvenation improves tissues at at the physiological and histological levels that are in the cells that are partially reprogrammed and the question why this is possible why you know Rejuvenation is possible during the reprogramming process I think we're just lucky that the reprogramming process is gradual both in the changing of cell identity and in the rejuvenating aspect and this slide shows like the two trajectories one trajectory of silencing the genes responsible for like fiberblast identity and another slid showing rejuvenating re Rejuvenation the the blue line is the epigenetic age of the cell and we see that this is a gradual process basically that cells are gradually reprogrammed they gradually are moved in the direction of embryonic stem cells and they're gradually rejuvenated and so there is some point like a therapeutic window B basically where we haven't yet reached the point of no return where the cell can no longer be a fiber blast cannot no longer do the function of the skin cell and yet at this still by then the cell has already been rejuvenated so we can if we stick to this therapeutic window we can push the cell just enough in the direction of embrionic stem cell but not too far so it's still a fiberblast but it's a rejuvenated fiberblast at least according to this research that looked into rejuvenating process and genetic age that happens during reprogramming and so this is what essentially what we're trying to harness thanks to this gradual nature of reprogramming we can find this window of safe partial reprogramming where we get Rejuvenation but we don't yet get the risks associated with the cell stop stopping doing its job and uh just to address another kind of a frequent point of criticism that Skeptics of partial Reaper bring up they often bring up this uh well-known fact that in vitro when you reprogram cells in a Peter dish only a small percentage of cells end up being fully reprogrammed to this F potency most of the cells do not and they kind of point to this and say well if only a few cells ever get to full reprogramming then only a few cells will ever be rejuvenated in Vivo and it's never going to be efficient enough as a process to be used as a Rejuvenation therapy for an already foreign organism but those people who actually study uh invivo uh inv vitra reprogramming they know or they know at least now they know that the initial stages of reprogramming are ex uh exerted on all cells and this initial opening up of Chromatin that happens happens in all the cells that have yaka factors activated in them and it's just that in most cells what happens later is chromatin is recondensed and it seems to be an active process preventing cells from being reprogrammed but if you actually disable this active process as this paper show this is one of the hisone hone 3 k36 if you want the details but if you disable that process then all of the cells in the feature dish actually make it all the way to cotesy so this implies that actually all of the cells experience the all of the cells exper experience reprogramming and in particular the early stages of reprogramming which are associated with Rejuvenation so we can expect for iniva reprogramming the cells to pretty much all the cells in which we activate the reprogramming genes to be rejuvenated to some degree because they all experience the initial stages of reprogramming and so the applications of this are quite profound basically uh as I mentioned in the beginning the problem with the aging process is or one of the problems is that it's exponential in increasing our mortality risk and so if we're able to somehow slow down this exponential increase or ideally would like to stop it or even reverse it then as I mentioned the like a person in in their 60s has one and 100 chance of dying within a year which is for a 60-year-old is is actually not too bad if we're able to freeze the aging process and stop it right there then the 60-year-old person just with this uh aspect of reprogramming just stops the increase in mortality risk just mathematically could potentially expect to live another 100 years and if we're able to reverse of course the aging process which I think partial reprogramming like repeated partial reprogramming can accomplish then we can then even rejuvenate people and decrease their mortality risk and of course while that's the ultimate goal we haven't gotten there yet we're just making kind of First Steps in this direction but I think there has been many promising steps in that direction since the 2016 or Campa paper and just want to highlight some of them in the next few slides that I think are particularly compelling for example this step that show that even a single B of partial reprogram can extend lifespan including in progeric mice and normal mice this paper the many of you have seen it from David Sinclair's group this is the famous paper where they were able to restore Vision in mice with partial reprogramming uh another paper showed that partial reprograming can improve muscle reg regeneration after injury wound healing also I mentioned in the beginning there's like a dozen different disease areas in which partial reprograming has been shown to be therapeutically effective and these slides just quickly go through them just because we don't have enough time if we had to Deep dive deep into all of them we need a couple hours uh this study showed that you can improve spinal dis degeneration with param this study looked at long-term safety of parti reprogramming showed that even a 10th 10 month long protocol of inducing IM manactors is not only safe but also therapeutically beneficial this is the same paper just another slide showing the results that with yet 10 month long period of induction in mice it was safe this study already mentioned uh in the beginning as I said Skeptics of partial reprogramming have pointed to Wild type mice as being kind of next measuring stick by which part partial reprogramming has Effectiveness has to be measured and U uh basically they were saying that because we haven't yet seen a life extension in normal mice then maybe partial reprogramming Life Extensions is an artifact of pric mice but this paper out of rejuvenate bio showed that actually gene therapy approach can greatly increase uh lifespan in not greatly but can increase lifespan in in normal mice and also there's been uh a few unpublished results I just came from a conference where people were reporting unpublished results and they're again very very promising because there group showing the parain can improve the brain in Vivo uh liver function cardiac function hematop stem cells and t- cell function and also the David Sinclair's group is pursuing an indication in the eye this eye stroke indication for using a gene therapy based on partial rogain to go into the clinic and it might be the first group to get partial rogain into the clinic okay finally let's talk about brain Rejuvenation and uh there's been also a lot of uh exploration of partial reprogramming in the brain as well including by ourselves one of the earlier studies from an alanus group who's been a pioneer of partial programming as as I showed in 2013 they've continued looking into it and they showed that partial reprograming can improve memory on the object recognition test and this is a very cool result very recent result of 2024 paper by Ares group from Stanford showing that reprogramming partial reprogramming can increase or induce neurogenesis in Old mice like basically generation of Novel neurons in the hyppocampus of old mice which has been a very uh kind of controversial aspect do we get can we have neurogenesis in adult brains and with at least with partial reprogramming it seems that we can another brain reprogramming company uh reprogramming paper from rolfa goya's group in Argentina showing that if you deliver gene therapy into the hippocampus of old rats in this case you can inre increase their cognitive performance and this is uh very similar to what we've done at youth we've delivered a gene therapy into the hyppocampus of uh old mice and also Alzheimer's mice and we also see positive results and U rolag Goya group saw improvements in cognitive tests and also saw reduction in epigenetic age of the rats treated by partial reprogramming they also done a different study on female fertility where they injected female rats in the hypothalamus with partial reprograming therapies and they showed that after after inducing partial reprogramming in that brain region that has positive effects on female fertility and moving on to alzheimer's my personal passion and of course the therapeutic focus of Youth bio uh there's from the very beginning we had good reasons to believe that Alzheimer's is a good indication for partial reprograming mainly because Alzheimer's has a strong epigenetic component to its ethology to to to the way Alzheimer's happens and basically gene expression in the brain cells of Alzheimer's patients can could actually be can explain why the disease progression happens as if you might remember since epigenetic changes are reversible we can be at least with some confidence expect that if we reverse the gene pattern the pattern of gene expression in the neurons of Alzheimer's patients we can expect if maybe even a reversal definitely slowing down of Alzheimer's symptoms may maybe even a reversal of Alzheimer's symptoms this was the theory now we have evidence in practice that this indeed seems to be the case this is a study in Alzheimer's mouth bottle showing that you can epigenetically prevent Alzheimer's then this is actually the study from 2019 that was the main inspiration for the hypothesis I just outlined basically showing that you can epigenetically reverse Alzheimer's symptoms in in a mouth model and basically it show that epigenetic modulation can like not only prevent the symptoms but can reverse them and this was what made me very optimistic that in patients we can observe the same reversal of symptoms using epigenic modulation by partial reprogramming and uh this is the paper I I gave a preview in the beginning and it seems that we're running out of time but I was very happy to see this this is a 2023 late result basically validating the same observations that we had at youth bio that parti reprogramming in Mouse model of Alzheimer's disease can have beneficial effects beneficial therapeutic effects on Alzheimer's might Alzheimer's symptoms and also not only at the cognitive testing level but also at the level of biomarkers they show that you can have lower levels of bet amalo which is a key biomarker of Alzheimer's disease lower plaque burden in in these mice and also on the cognitive test of course those mice also showed better performance in those tests and this observ of this group validate our observations which were very similar we saw a reduction bet amalo and we saw an improvement in cognitive tests in the in the mice and I briefly wanted to go over our results but it seems that I have only about five minutes but um basically our our main approach was our main tenant behind youp is that we need to be cell typ specific that uh you have to have specificity in terms of triggering partial reprogramming in in different cell types and this was validated by Alandra Campo who's if you remember was the pioneer of partial reprogramming and uh he's also our collaborator but he showed that if you avoid the liver and the small intestine you can push reprogramming for up to 10 days of consecutive expression of reprogramming factors and the all of mice survive but if you don't if you keep uh uh reprogramming the liver in the small intestine then the mice start dying after day four and basically this necessitates the cell type specific approach to reprogramming that you have to avoid certain tissues and this means that from our standpoint we can be also targeted in the cells that we induce partial reprograming in with the U different cell types listed here and of course neuronal cell types are our first priority with Alzheimer's being the first indication and relative to other companies we're already finished for animal studies so we're quite uh far ahead of our uh peers in terms of getting to the clinic and getting to clinical validation of param our first indication is Alzheimer's disease and there's I already mentioned there's good reasons from a scientific standpoint there's good reasons from regulatory standpoint why Alzheimer's disease is a good indication for Alzheimer's and our first animal study was as a proof of concept to show that we can deliver our therapeutic constructs to the brain and activate them in brain and get the expression of these factors in the brain and once we validated that with we went into three different disease models with Alzheimer's pereria and age related cognitive decline being the three models and we saw positive results in in those tests and I'm getting the signal that we're getting short on time and but basically yeah switching kind our Focus from the past to the Future the important factors in translating partial reprogramming they're listed on this slide and I think one of the main aspects is delivery and this is really the the the last interesting aspect of the presentation that I'll go into because a lot of people think delivery to the brain is a like insurmountable challenge but actually there's a lot of precedent in Parkinson's and gen already actually talked about this in Direct Delivery of therapies to the brain including cell therapies and Gene therapies and this slide lists like a dozen different Gene therapies that have been directly delivered to the brains of Alzheimer's patients by direct injection into substantial neiger and so uh also this has been shown in Alzheimer's disease as well that you can deliver into the hippocampus or Le very close to the hippocampus gene therapy and this was a 2013 study which then they had a follow up like 7even years later showing that the patients that had this injection into their brain had sustainable expression of the delivered construct for like up to seven years which makes me very optimistic that if our constructs that we deliver to the brain can also be expected to be very long lasting and there this is another paper showing the same uh precedent of Direct Delivery into the brain uh as I mentioned this just said that's the precedent that this delivery is possible but of course uh invasive delivery is is not great if we can avoid sticking inle into patient brain we should and for that there's now this concept of ultrasound guided delivery where it's a non-invasive method of getting things to the brain and this table lists like many different different Mouse models of diseases in which this approach has been tried and Beyond Mouse models it was also demonstrated in patients already this was the Toronto uh sick kids U Hospital study that showed that you can have successful delivery into the brain of pediatric patients using ultrasound guided delivery and I won't get into this slide just for the interest of time but basically future directions of partial reprogramming that are listed here uh I think we're well on our way of finding finding Noble factors some companies are dedicated to finding Noble factors that are not as risky as IM Manaka factors new limit shift bio their main mission is to find new factors and I think we'll need tissue specific and cell type specific factors that will be most effective in a given cell type and for that you also need cell type specific delivery mechanism which I think the field is also exploring and uh so in closing I just want to say that I'm very optimistic that uh both par reprogramming and brain Rejuvenation by par reprogramming will get to the clinic very soon and I just want to close with this quote from Dr b w after they published the seminal ampa paper with careful modulation aging might be reversed and I believe that with par programing we're well on our way to figuring out just how to reverse the aging process thank you very much and uh | ↗ |
| 25 | Axial | Scientist Stories: Shinya Yamanaka, Cell reprogramming and Pioneering ... | 21524 | 628 | 34 | 68.9 | positive | 16:31 | so good morning everybody it is a great honor to be here today so before starting my own talk I want to know uh General background of the audience so uh how many of you are working on life science or biology please raise your hand oh 90 I said how about physics or space ah I see uh how many mathematicians are there oh I see it's very very good to know thank you thank you so I'm gonna have my first slide please uh anyway so I I I started my career as a physician surgeon 30 years ago in 18 1987. I'm not that old and actually it was my father who talked me into medicine I respected him a lot however as soon as I became a doctor within a year my father passed away he suffered from hepatitis C after transfusion so you know as a young doctor I was not able to do anything to my own father I couldn't help him that was the biggest reason why I decided to become a scientist I wanted to become a scientist who overcomes diseases so as you know science has overcome hepatitis C we now have a cure for Hepatitis C however there are many other diseases that science still need to overcome this is just a few examples like Parkinson's disease blindness heart failure these are all very serious conditions terrible however if you think about the cause of these diseases and injuries it's rather simple they are caused by a loss of function of just one type of cell or maybe two one or just a few type of cells for example Parkinson's disease is caused by a loss of function of dopaminergic neuron blindness is caused by loss of function retinal or corneal cells heart failure is caused by the subfunction of cardiac myocytes it's only one type if we scientists can prepare this type of cells in a large quantity and if we can transplant these cells into patients we should be able to help patients we should be able to bring functional recovery to those patients however as you know it is next impossible to obtain a large amount of human cells but now we can do it at least sincerely we can do it by using this new type of stem cells induced peripotent stem cells IPS cells IPS cells have two important properties first oh I'm sorry IPS cells we generated this technology 10 years ago 2006 fast in mice and then in 2007 in human it's very simple all we need is a combination of four transcription factors by putting these four factors all together into your own skin cells or blood cells we can make your own IPS cells from each of you IPS cells can grow infinitely we can expand as much as we want furthermore from IPS cells we can make many types of cells that exist in a body like brain cells heart cells liver cells in a large quantity by using this technology now we can prepare a large amount of dopaminergic neuron retinal cells heart cells so that we can help many patients many scientists Vision scientists all over the world have been working on this application of ips cells for example Dr martial Takahashi a good friend of mine in Japan she has already studied clinical trial using human IPS cells two years ago for patients suffering from age-related macular degeneration it's a brightness caused by a loss of function of just one type of cells in retina she can now make that type of retinal cells from Human IPS cells and she depressed patients on injured aged cells with newly developed retinal cells from IPS cells it's been two years and the patient has been doing very well Dr June Takahashi he happens to be the husband of Takashi just coincidence but he has been working on Parkinson's disease he can now make a very pure functional dopamine magic neuron from Human IPS cells he is now testing this strategy in monkey and we're hoping that he can bring this finding to Human as early as next year another friend of mine colleague Dr coach Ito can make functional plate rates as well as erythrophytes from Human IPS cells you know countries like Japan we are aging Society we are going to have more and more elderly people who need blood transfusion but we are going to have less and less children who can donate their blood so only after like in five years we will be in huge trouble we won't have enough red Donuts so we need to do something alternative this ipso based uh method is a good alternative to blood transfusion this is also very close to clinical trial because in terms of safeness it's very safe no plate rates erythrocytes they don't have they don't grow they don't have nucleus so we don't have to but we don't need to worry about tomorrow Dynasty in this application so this is very safe also we are fighting with Cancers with IPS cells by combining IPS cell technology with cancer immune or therapy we can make T cells from IPS cells and in IPS cells by using crispr we can modify the Genome of ips cells to whatever we want for example we can introduce a T Cell receptor Gene that can recognize cancer specific antigen and from those modified IPS cells we can prepare a large quantity of cancer attacking T cells in this way we hope that we can overcome cancer at least some forms of cancers well at least in theory we can make IPS cells from each individual patient autologous transplantation but in reality it takes very long and more importantly it's very expensive we helped Marcel Takahashi in her first clinical trial we did genome analysis just for one patient we spent almost a half million US dollars so it's just too expensive in order to overcome this practical issue we have been working on so-called ipsl stocks so we are now making IPS cells from healthy volunteers instead of each individual patient however it's not autologous so we need to overcome immune rejection the best way to minimize immune rejection is to match its array however HLA is so diverse none of you in this audience has the same HLA and this we have identical twin in this room so here I saw the HRA prototype of 10 individuals by color none of these 10 indivisible or cells have the same color combination so if we want to prepare ipsl stock that can match these 10 patients with HLA we need to prepare all 10 HLA combination if thousands we need to prepare thousand ipsl stocks it's too much but if we can identify this kind of HLA homozygous donor the situation is very different because just making one good IPS line from this HLA homozygous donor just one donor we can cover 4 out of 10 individuals shown by arrows because these four individuals have read and something else as long as he or she received red from the HLA homozygous toner they cannot distinguish transplanted cells from their own cells based on this model we have we and others have calculated how many Etc homozygous Donuts are required to cover large population this is just some examples in Japan we have calculated 140 Etc homozygous donors can cover up to 90 percent of all the Japanese population that means 140 civil lines can cover 100 million Japanese people in the states it's a bit more diverse but still 100 super donors Etc homozygous donors can cover 78 percent of European Americans 63 Asians 52 Hispanics 45 African Americans in UK it's very similar to to Japan so many countries including us are now working on this HCA stock project I have 20 seconds Okay so so today I only talk about cell therapy but there is another important medical application of this technology we can use these cells from patients like brain cells from Parkinson's disease patients or heart cells from heart disease patient in order to understand in order to make disease models and in order to perform direct screening so cell therapy and disease modeling drug screening are the two important medical applications of this technology I really hope that in next decade 10 years we can realize many of these applications so that we can overcome many more diseases so thank you very much again thank you action there's time for some questions uh anybody from the audience we have time for some questions so we should use it oh yes sorry you mentioned clinical trials in Japan are you familiar with clinical trials here in the states involving some of these applications yes in in the states as you know or clinical trial using human esls have already started and we have been talking to them so that we can collaborate with each other and maybe some of their applications May uh move from es to IPS cells another question yes oh that that's that's a very important point so uh I don't think we can eliminate immune rejection just by using HLA homozygous donors as you said natural killer cells should recognize those cells because they don't have one Etc hypotype so uh even using uh homozygous donut we still need to use some immunosuppressants but we hope we can decrease the dosage and kinds of immunosuppressants all right that's the last question then there over there is there any prospect that the Regulatory Agencies will see the wisdom of this particular model and instead of testing drugs on rats Apes Etc we'll use this as a screening process to eliminate it's it's also yes efficacy versus toxicity yes especially toxicity you know pharmaceutical companies has been using like dogs or the other animals or cancer cells in predicting cardiac togetistic but now we can make beating cardiac myocytes so actually many pharmaceutical companies have been working on how to use these cells in their own safety tests but we still need to talk about regulatory body because it's a huge change from uh conventional test so you know in order to test in order to change that kind of uh stereotypic conventional test it's it's been very difficult but but I I hope we can depress uh in in the near future in next 10 years all right well thank you very much okay thank you very much [Applause] | ↗ |
| 26 | Dr. William Li | "Try It For 1 Week" - Most Effective Way To REVERSE AGING IN DAYS! I D... | 67749 | 3116 | 226 | 68.4 | positive | 23:58 | No transcript | ↗ |
| 27 | University of California Television (UCTV) | Cellular Reprogramming in Human Disease | 2740 | 113 | 4 | 67.8 | neutral | 58:26 | What I thought I would
do today is focus on a theme that I
think has evolved in our laboratory
where we can begin to both understand disease
and impact disease through the lens of
reprogramming cells either to do what
we want them to do or to recognize that in
certain disease states, the basis for disease is actually a cellular
reprogramming event, and once we understand that, that provides avenues for
potential intervention. I am trained as a
pediatric cardiologist, so my comments will be largely focused through the
lens of heart disease. But I do want to emphasize that the conceptual framework and the approaches could be applied, I think, to most human diseases. With regards to heart disease, of course, this remains the
number one killer worldwide, and we've gotten
better at keeping people actually alive
after acute events, but the end result
of that has been a growing population
that are left with damaged hearts and
what we call heart failure, clinically, and there are over 25 million people now worldwide who suffer
from heart failure. Ultimately, these
individuals would require a heart transplant, but even in the United States, there are only about 3,000 heart transplants done per year, and many countries don't
have any available at all. On the other end of the age spectrum is congenital
heart malformations, where children are born
with malformed hearts, and this is the most
common human birth defect. It occurs in 1% of all live
births across the world. It's a huge number. Here, too, we've
gotten better at palliating those defects
and keeping children alive, and as they get older, we're beginning to see a
number of sequelae that happen as they get older into adult life, including
heart failure, but also as I'll show you, we believe that some of the same genetic
abnormalities that result in malformations affect homeostasis
of the organ later on. My laboratory has over the years focused on trying to
deeply understand the gene networks
that are at play in cardiac sulfate
decisions early on and subsequent morphogenetic
events with the notion that we could utilize that knowledge
in two distinct ways. One, to regenerate
damaged hearts, and I'll show you a few
examples of approaches we've taken harnessing the cells
that are already in the organ, either the fibroblast population or the cardiomyocyte
population itself. Also that we could use this developmental
biology knowledge to understand the genetic
basis for heart disease, and not only understand that, but decipher
mechanism that would lead to new therapeutic
modalities, and I'll show you
an example of that. Now to start with the
regenerative area, we've published a body of
literature in this space, and I want to just in the
next few slides summarize for you some of what
we've learned from that, and I'll spend the
bulk of the time of this talk focusing
more on genetics. But in this realm, we've taken two
approaches to try to create new muscle in
the heart after damage. I should say that many
other groups are trying to transplant pluripotent stem cell derived cardiomyocytes
into the heart, and I'm very hopeful
that we'll, as a field, be able to overcome some of the current hurdles with that, and I'm eager to
see those develop. Our laboratory took a
different approach, and we decided to ask if we
could get the cells that are already in the organ to do something they
don't normally do. One thing that they
don't normally do, which is why the heart has little to no capacity
to regenerate, is they permanently exit the cell cycle very
soon after birth, and the result of that is
that if the muscle is lost, there's literally
no replenishment. Some years ago, we found a
way to quite efficiently get these adult
cardiomyocytes to re-enter the cell
cycle and divide, and that is one approach that we're pursuing to
regenerate the heart. The other is to harness the fibroblast population
that's in the heart and reprogram them directly into new
cardiomyocyte-like cells. Now, on this front, what we reported some years ago
was that a combination of four cell cycle regulators that are all highly
expressed during fetal development
when the heart is dividing and all get down
regulated soon after birth, if we reactivated those and stimulated both G1/S transition, as well as a G2/M transition, we could get 15-20% of adult myocytes in vivo to
re-enter the cell cycle, and that was enough to
increase cardiac output and improve function
in animal models. The important thing
here we found is that if you had
all four factors, you got stable cell division. What I mean by that is if
we remove any one of them, the cells actually could
divide in many cases, but then they'd undergo
mitotic catastrophe very quickly and
kill themselves. This is very encouraging
but for these experiments, we had delivered these
factors with the virus. That we presumed early on was a non-starter for
clinical translation because, of course, these could
also be oncogenic. We had tried years ago
to deliver this as mRNA, although one of the
problems with mRNA is that they only create protein for about three or
four days at the most. That was perfect for this
application where you want these cell cycle regulators
there for a few days. The cells divide and then
you want it to be gone. It turned out that
we could never get good delivery or expression, and it turned out that when the COVID
vaccine was developed, what many people don't realize
is the mRNA technology, of course, was quite old, but what made that possible
was new advances in lipid nanoparticle technology that allowed better delivery. With that in mind, we
visited this idea recently, and in collaboration
with Kevin Healy and Niren Murthy's laboratories at UC Berkeley in the
bioengineering department, we've screened for new LNPs
that might have tropism or propensity to deliver payloads specifically to the heart and specifically in areas of injury. What I'm showing you here
is an LNP we've found recently that has been injected systemically into
a reporter mouse where we're delivering mRNA of cre recombinase and if
the proteins expressed, you get a fluorescent
red marker activated. This is the heart here with the light sheet microscopy and I'm going to play a movie for you, and you can see at the
apex is where there's been damage after
coronary occlusion. You can see there's
accumulation of cre recombinase
protein depicted by the red here in this area
of damage specifically, and this is with the
whole body deliver. If you zoom in, you can see many of these cells
are actually quite large, and those are the
cardiomyocytes that we've documented in other ways, and you also see
these small cells which are the fibroblast cells. We believe we have a pretty
good delivery system now, and we're revisiting the ability to stimulate
proliferation and improve cardiac output with delivery of those cell cycle regulators
with this lipid nanoparticle. We're awaiting results for that, but we think at least we have a good delivery mechanism that's non-viral
now for the heart. Now, the other approach that
I mentioned is after injury, this heart that you
see here in purple is all the scar tissue that has replaced the viable myocytes. It turns out that the
cells, of course, that make this scar tissue
or the fibroblast pool, which turns out
to make up 50% of the heart in both
animals and in humans. These fibroblasts are also the ones that make scar tissue. Some years ago, we asked, could we utilize our
developmental biology knowledge when nature is making
heart cells and redeploy cues into these
adult fibroblasts that are already in the heart
and convert them to be more cardiac myocyte-like. In fact, we were able
to with the combination of essential developmental
transcription factors, particularly GATA4, MEF2C, and TBX5, and together
those three proteins, we found could bind to DNA in
a combinatorial code across the genome and wholesale
switch the epigenetics of an adult fibroblast to
be more cardiomyocyte-like. In mice, rats, and in pigs, we could do this with
enough efficiency, particularly in vivo, to improve cardiac output. Importantly, these cells electrically coupled
with their neighbors, which was essential for to
get a coordinated contraction in the heart so that
you can improve cardiac output and
not have arrhythmias, which has been a problem with transplanted cardiac
cells. That was great. We had the conceptual framework
for this reprogramming. But in fact, these three
factors did not fit into a single AAV that would be the best delivery
vehicle for this, and there was much work to be done to really translate this. Years ago, we put this
into a company we call Tenaya Therapeutics
in South San Francisco, and they've raised
a lot of money over the years to try to
move this forward and done a tremendous amount
of work to narrow the genetic material to
fit into a single AAV, develop a novel
capsid that could efficiently infect fibro blasts, not just not myocytes and a variety of other
delivery hurdles. They've done that, and I'm going to show
you just one side of data from Tenaya where they've done a coronary occlusion
in this pig heart, which is similar to human. You can see here at the bottom, this heart gets blanched. It's the area of damage. Then they waited a month to let the function decrease and
stabilize in the pigs. The ejection fraction of the
fraction of blood that is pumped out of the heart with every beat has gone down from, say, 60%, which is
normal to about 30%. Then they administer
the therapeutic after that one month post
myocardial infarction. What I'm showing you here is the data over a
two months period after delivering the dose compared to control pigs
who got a control vector. You can see here in the
control pigs in gray, the function stayed about flat, which is what we'd expect. They've already stabilized
their decrement. In contrast in the blue lines, you can see that
these pigs went from about 30% to low 40s,
which isn't normal. But it's enough to get out of the conversation of whether or not one should be considering
a heart transplant. Enough, people can walk
up a flight of stairs. They can walk several blocks, and so that essentially
is the goal here. Tonight has a number of other
hurdles still overcome, particularly with a
non-invasive delivery method that they're
continuing to pursue. But what I've tried
to share with you in this part is how in both cases, if we understand the gene
networks at play well enough, we can imagine ways to
re-program those cells to do something that they
don't normally do that could lead to
regenerative repair. Now, one of the things that I won't spend
much time today on, but I'll just briefly in one
slide in a cartoon form, summarize our recent findings that I'm also excited
about is the fact that even if you don't lose
any more myocytes and when somebody
has heart failure, what we do know is that
they reliably continue to decline in cardiac
function over time. The reason for that is this cardiac
fibroblast population gets inappropriately
activated and lays down more and more
fibrotic tissue throughout the heart globally and that
impairs cardiac function. In a body of work
in our lab led by two very talented postdoc who are both running their
own laboratories. Now, Michael Alexanian
and Arun Padmanabhan they started to investigate how is it that the heart senses this stress
that it's under, and how does it then signal to activate these fibroblasts
to become profibrotic? It's really quite
interesting what they found, which is that they
were able to map a very specific stress
dependent enhancer in the macrophage
population in the heart. These, we believe are the
sensing cells of stress. This enhancer activates
a number of cytokines, including maybe most
importantly interleukin-1 Beta. Interleukin-1 Beta is then
secreted and received by a specific receptor on
neighboring fibroblast, and that signaling pathway
then they mapped to another very specific
stress dependent enhancer that activates a transcription
factor they discovered Meox1 that turns out to
be the master regulator of a transcriptional switch
taking a fibroblast from a quiescent state into
an activated state. The reason I think
it's important they were able to trace
all these steps is each of these then serves as a potential
target to go after therapeutically either
an antibody against interleukin Beta
that they have shown is functional or deletion, or blocking of this enhancer, or this transcriptional switch. Each of these gives
you a level of specificity that we believe will reduce the potential
off target effects of, say, just blocking the
pathway completely. Especially if we can
intervene at the enhancers that are only active
during stress. That's all I'm going to say
about this part of the work, but we are very excited about
this potential to arrest, at least the cardiac function, so it doesn't continue
this decline. Now, for the remainder
of the talk, I'd like to focus on our efforts at understanding
genetics of heart disease. Here, also, our laboratory has published a body of
literature over time. I want to focus today
on two stories. One that represents a long
arc of investigation in my laboratory and the other that is more
recent unpublished work. The first is related to
this specific form of heart disease that
turns out to be the third most common form
of adult heart disease. It involves specifically the
aortic valve in the heart, which separates the left
ventricle from the body. What happens in a
large number of people is that this
aortic valve gets calcified over time
and doesn't open and close properly and ultimately, needs surgical replacement. It's an age dependent
phenomenon, so the incidence increases
as people get older. Interestingly, there is a link to a congenital
defect that occurs in a sub population of this
where some people are born. Instead of having three
nice valve leaflets that form this nice
Mercedes sign, as you see here, they're born with only two
aortic valve leaflets. Most of the time, they don't even
know they have it. But as they get older, about a third of these
individuals will develop early and more
aggressive calcification. It turns out that 1-2%
of the entire population worldwide is born with the
bicuspid aortic valve. But like I said,
most don't even know it until later decades in life. But sometimes, the valve is so malformed that even
in the newborn period. Children have difficulty
with blood getting out of the heart and they need an acute intervention
to stay alive. It's a whole spectrum of disease from fetal or childhood
to adult onset. The genetic cause
of this disease had not been known until
some years ago, when I took care of the little
boy here at the bottom of this family tree when I was
in UT Southwestern in Dallas. That boy was newborn and had severe erratic
valve stenosis from this thick erratic valve that we had to put a catheter across, blow up a balloon, rip it open, and then
he was able to survive. But what was interesting is
upon taking a family history, it turned out there
multiple generations of individuals indicated in
these black circles or squares that had already had open heart surgery because of calcified ertic
valve leaflets. This is clearly autosomal
dominant in transmission, meaning it's likely a
monogenic disorder, and we were able
to even back then map the single gene
that was causing this, and it turned out
that this disease in this family was caused
by a heterozygous, loss of function
mutation in NOTCH1. NOTCH1, I'm sure, is very
familiar to all of you. It's a famously studied gene. It's important in development
of almost every organ in our body and in some
maintenance in the adult. It was curious that reducing the dose of
the protein by 50%, which is what happens here, was caused disease just in the erratic valve
and nowhere else. Since then, our lab and many
other groups have identified a number of individuals and families with NOTCH mutations, ranging from erratic valve
calcification in the adult, all the way to even fetuses, that have such a severe
erratic valve obstruction in utero that their left ventricle doesn't even form as a fetus, and they are born with a very severe congenital heart lesion, missing a whole
chamber of the heart. That was great. This is our
first known genetic cause of this common disease. We were very excited,
and we thought, now we can begin
to understand it, but then we hit a roadblock. Mice that were heterozygous
for NOTCH, which, of course, had been made
much earlier were normal. Homozygous small mice died
at embryonic day 9.5 from vascular failure
because NOTCH is also on the end of the lining
of the whole vasculature. This became a nice to know, but we had very little
idea of mechanism. If you don't know mechanism, you can't really do much about it. I should say that this
smaller family here back at that time was
contributed by Paul Grossfeld, who's here at UC San Diego as a pediatric cardiologist and collaborated with us on
this work years ago. We had a breakthrough, though,
because Shinya Yamanaka, I had just recruited
after I moved to Gladstone to come to establish a laboratory
at Gladstone in 2007. He had described how to
make human iPS cells. We immediately flew the
family members from Dallas up to San Francisco
and did skin biopsies, made iPSL lines from four patients with the
mutation, four without. We turned those into
endothelial cells because we knew that those
were the culprit cells. I'd say for years,
we learned nothing. The reason any of you who try to model disease know
that unless you have isogenic controls and you've controlled the rest
of the genome, there's too much noise in the system to figure
these things out. It wasn't until we
were able to do gene editing
efficiently and make isogenic lines and then did full omic studies of
where NOTCH binds to DNA in the mutant setting, how it affects the epigenetics, and the transcriptomics
that finally the biology laid itself
out beautifully. This work was led by
Christina Theodoris, who was a very talented
MD PhD student in our laboratory at the time and went on to train in pediatric genetics at
Boston Children's, and we've now recruited to start her own laboratory at Gladstone. What Christina found back then, is that NOTCHs normal job in
the heart turns out to be to block the valve cells from turning into
osteoblast like cells. That's its job is to put
a brake on this system. You may ask, why would nature set it up that there
would have to be a gene to block this
sulfate transition, which is essentially a
cellular reprogramming event. It turns out that
cardiac valves are not that different in their
tissue compared to cartilage. Nature has used many of the same gene networks
that it uses to make cartilage to make cardiac valves during
embryogenesis. But it doesn't want
it to go all the way to become bone like, and so NOTCH is there to
put the brakes on that. It seems like the crux of this very common disease
is quite simple. It's a cellular reprogramming
defect where the cells are changing their fate and losing their identity and
becoming osteoblast like. Not only did Christina
figure that out, but since she started
off by mapping broadly the gene networks
that were shifting, what she found is that these gene networks
were largely being driven by upregulation of just three key transcription
factors, SOX7, TCF4, which mediates Wnt
signaling and SMAD1, which mediates BMP signaling. If there are about
1,000 genes that were dysregulated in
the sulfate transition, and about 80% of those
are 800 were directly, indirectly or indirectly
related to these three factors, and that if she
knocked those down, these three factors down, you could largely shift
the network back. That was great. Now we understood
mechanism a bit and it looked like it funneled
down to a discrete pathway. Christina decided to undertake a very interesting drug screen, not looking for molecules
that upregulated NOTCH, but rather molecules that
would shift the whole network. The whole gene network
closer to normal, and she set up a machine
learning algorithm back then to call normal cells or
mutant cells and ask if thousands of molecules, if any of one of them would
shift the whole network back. I won't go through the details
of that as it's published, but suffice it to
say she did find a very interesting
small molecule that seemed to correct the whole gene network
quite effectively. This molecule turned out to be an estrogen receptor
related Alpha inhibitor. We validated that as a target subsequently with
SINA experiments and testing a host of
other small molecules that also hit this target, and we're convinced
now that this is in fact the true target. That was great.
We've now finally, after these years of effort, had a small molecule that
might actually be able to shift this
aberrant gene network back closer to normal. But you'll recall that we didn't have a mouse model
to test this in, and we weren't going to go
from a human iPS model, to a clinical trial, of course. Christina had the clever idea that putting together
a few observations, and one is that, as I mentioned, this is an age
dependent disease. We know that telomeres get
shorter as people age, and we also knew that mice have much longer telomeres
than humans. She asked whether mice
might be protected from the disease simply because
of their longer telomeres. That's a testable hypothesis. She tested that by
crossing NOTCH1 one heterozygous mice that were normal with mice lacking TERC, which is the RNA
component of telomerase. When you do this in each
generation of breeding, the telomeres get
shorter and shorter. It turns out that just in the second generation where the telomeres are just
a little bit shorter, that resulted in nearly
complete recapitulation of the human phenotype. It's really quite striking. I'm showing you that here in a cross-section through the
aortic valve of these mice, just after a month of age. It's really quite rapid. On the top panels, what you see are the three
nice aortic valve leaflets and a normal mouse
that's turk null, but not wild type. In contrast, you can
see on the bottom that these valves
are very thick, and they're heavily calcified, as indicated by
Alizarin Red here. This is what we see in humans and by ultrasound in these mice, we can detect the
level of stenosis, which is exactly the way
we detected in humans, where if the valve
aperture gets narrow, blood has to go across
it faster in order to get the same
amount of blood out to support the circulation. You can measure the speed
of blood across there, and that tells you how
much stenosis there is. But what this mouse model also allowed us to do
is to go back and ask if that observation in vitro was really
happening in Vivo, namely, are these
cells undergoing a sulfate switch to become
more osteoblast like in vivo. For that, Christina
stained these with valves with a marker of
osteoblast called Runx2, which is a master
transcriptional regulator that drives the fate even
and you can, I think, easily appreciate here
that these cells are all positive for Runx2
suggesting that, in fact, this is likely a disease of cellular
reprogramming. This mouse model then
gave us a way to test this drug in vivo in the setting of erratic
valve stenosis. We recognize that most
in the human population, these individuals would come to the attention of a physician you can hear the level of stenosis
with the stethoscope. Then normally what we
do right now is that we detect that and see it by
ultrasound, document it, and then we just watch
people over years, and as it gets worse and worse, then we do surgical
intervention. The reason for that is
that right now there's no medical therapy whatsoever
for this condition. What we did in mice
is we took the mice, I should say this was
incompletely penetrant, so not all the mice had a degree of stenosis that we
could detect by ultrasound. We did ultrasounds at a month of age and
isolated those with documented aortic valve stenosis and then randomized those in a preclinical trial to
either drug or placebo. Then we treated
them for a month, and then came back and repeated the ultrasounds after
one month and asked, did this drug slow
down progression? Because in humans, I think
all we would have to do is slow down progression,
not even arrest it. Because it's a disease of aging, most people will
ultimately succumb to other conditions rather than need an intervention for this. What I'm showing you
here the results from the placebo group,
the control group, and on the y-axis is the amount percent change over that one-month period of the degree of aortic
valve stenosis. You can see it's a
rather wide range, but most of them are
progressing as we'd expect, just in a month with a mean of somewhere around 80%
further stenosis. Now, in stark contrast, when we looked at the cohort of mice that had been treated, it looked something like this. While there are a couple
of mice that did progress, the vast majority had
little to no progression. But most strikingly, half of the mice actually
had regression. It looks like with this drug, we're actually also able
to not just stop but maybe even reverse in part some of the
degree of stenosis. This is really exciting. We
think we might actually have a drug that could be effective
for this common disease. But everything I've shown
you so far is related to animals with notch mutations. It turns out that I
think I didn't mention this probably only 4-5% of the population with this
disease will present with mutations and not
your pathway members. Those are going to be
more rare conditions. Most people will not have an identifiable
genetic condition, even though it's
likely a combination of factors leading
to this disease. But we do believe
that for most people, even if they don't
have notch mutations, the cause of the disease
is going to be similar, which is a shift
of cell identity into an osteoblast-like fate and then laying down of calcium. We decided to test this
idea by collecting primary aortic valve
endothelial cells from patients who had had their valve explanted
at time of surgery, and normally the surgeons
would throw in the trash. We could get those and grow these actual aortic human cells. We did that for a bunch
of normal valves, a number of calcified
three-leaflet valves, and calcified
two-leaflet valves. The first thing we observed
by sequencing their RNA is that the same gene
network was shifted, and in particular, the same
three transcriptional drivers were all upregulated. That suggested that, yes, the same network
is being altered even in the absence
of notch mutations. Most importantly, the
same ERR-Alpha inhibitor restored the gene network
broadly and in particular, these three
transcription factors. With this information, what
we do believe we have now is a viable drug that can be taken forward
in clinical trials. I should say we've advanced the chemistry of this molecule, so it's got high potency
and low toxicity, features, and good pKa values. Our vision now is that we finally may have an oral
once-a-day drug that could be used to at
least slow down and arrest the progression of
this very common disease. That story, I should say, as a physician scientists, particularly, probably
represents one of the most satisfying arcs
of discovery of my career, going from taking
care of a patient to identifying the genetic cause,
understanding mechanism, and actually having a
potential therapeutic that could alter the way we
treat this disease. The last story I want
to share with you is, again, related to genetics, but it is an unpublished
story related to understanding why
congenital lesions occur. I should first say
that as a result of a broad nationwide consortium
funded by the NHLBI, where we've sequenced over 5,000 children and their parents
with congenital heart disease. We can now understand with a genetic basis about half
of congenital heart defects, which is a big
advancement for us. That still leaves
about half that are in this pie chart that
are unknown causes, and we're still working on. But even amongst the half
that wet "understand', I want to draw your attention
to this light blue pie. That is the pie where we understand the cause
because of aneuploidies. Now, that gives us some satisfaction that we
understand the genetic basis, but aneuploidy is often involve large portions
of the chromosome. Actually, we generally
don't understand the specific genes that
might be driving this. Again, if you don't
understand mechanism, there's not a lot we can do. Of course, the most
common of all of these aneuploidies
is trisomy-21, which results in down syndrome. It turns out that children
with Down syndrome, about half of them are
born with cardiac defects, mostly of the septal
defects where the walls between the atria and ventricles have holes in them, and there's communication of
blood between the chambers. Now, there's one very
specific type of septal defect that I've
illustrated here in this cartoon, which is at the level of where the separation is between the atrial chambers at the top and the ventricular
chambers here, involves the valves
that separate these. Here, there's free communication between all four
chambers in what we call an atrioventricular
septal defect because of a defect at this
specific level of the heart. This happens in children
without Down syndrome also, but in Down syndrome, this occurs with a thousand-fold
increase incidence, thousand-fold. There's clearly something
very specific going on here in trisomy-21 that is resulting in this specific area of the
heart being affected. We haven't known the genetic
cause of this in the past. This is the problem
that Sanjeev Ranade, a postdoc fellow
in the laboratory, undertook several years ago, and Sanjeev is now here at the Sanford Burnham Institute
running his own laboratory. I want to share with you the
beautiful work that he's done while he was in the lab and is continuing
here in his own laboratory. The question obviously is,
what are the gene or genes on chromosome 21 that are
driving this type of defect? Before I share with
you the story, there's one piece of developmental biology
background you need to know, which is that if you look at
a developing mouse embryo, like you see here from the side, here's the left ventricle,
the left atrium, and this is the
region that's between the atrium ventricular
chambers that we call the atrioventricular canal. If you do a cross-section
through this, you can easily see that the
muscle has a cuff around this specific area is different from the
neighboring muscle in the ventricle and atria. You can see that by
gene expression of this transcription factor, Tbx2, where it's only expressed in this cuff of muscle
and not here, in contrast to other
genes that are only expressed in the
chamber myocardium, but not this
atrioventricular myocardium. This is a very
specialized muscle right around where the valves will form and the
septa will form, separating the chambers, and is exactly where the
defect occurs in this disease. The approach Sanjeev
took was to use iPS cells that were made
from people walking around who are mosaic
for trisomy 21. These people don't
have any disease. They have a higher
risk of having an offspring with trisomy
21, but they're fine. But when you make iPS
cells from these mosaics, in the same dish, you'll get disomic iPS lines and trisomic. Again, the key is this gives
you isogenic controls. He did that and
differentiated them to cardiomyocytes and did
single-cell RNA sequencing. Here we can annotate cells shown here that are
actually of the type, specifically of the
atrioventricular myocardium, and others that are
ventricular myocardium. We can distinguish
by single cell RNA seek this specialized
population. Here's what I thought was a really key observation that made the rest of
the project possible. That is when you look at just the transcriptome
in these specific cells, there was a very
clear difference between disomic and
trisomic cells. That's illustrated
here in the dot plot of a number of genes, where you can clearly
see the pattern is different between
disomic and trisomic. Importantly, what
we observed is that the genes that
were normally high in the atrioventricular
canal myocardium, the specialized myocardium,
were all downregulated. In contrast, the genes
that were normally low, ventricular myocardial
genes, were now upregulated. What it seemed like
was going on here is maybe this disease
is one of, again, reprogramming in part of the specialized
myocardium to now be more like ventricular
myocardium, and that could be the
crux of the disease. Now this gives us an assay to
go after where some gene or genes on chromosome 21 must be causing
this pattern shift. Now the problem
becomes quite simple, although it was a lot
of work to find it, but conceptually it's simple. We were aiding in the fact that chromosome 21 is one of
the smaller chromosomes. There are 241 genes, and then there had been
a mouse model already made of trisomy 21 with
a syntenic region, and that model recapitulates the cardiac defects and only had duplication of less
than 150 genes. It must be one or more of those genes because we are
seeing the cardiac defect. I should say, from the
mouse data genetics, it was clear that they're likely at least two loci that both need to be duplicated to be
sufficient for the defect, but each being necessary. Then our laboratory had
over the years made a mouse atlas of all the genes expressed during the heart
during development, and of these 148 genes, only 66 were ever expressed in any cell
type in the heart, and so we figured
it had to be those since the mouse also
has the defect. That got it down to a
more narrow number. What Sanjeev decided to
do is take advantage of the CRISPR-Activation
approach. Now, any of you have done CRISPR-A know that
the problem with CRISPR-A is that you don't ever get really high
levels of activation. You get maybe 50%, maybe 100%, but you
don't get t10-fold. But for us, that was
perfect because in trisomy we were only
getting 50% activation. Sanjeev inserted the
Cas9 VPR cassette into the disomic line so he could use guide RNAs to each of
the 66 genes and ask, do any of the guide RNAs then recapitulate that pattern
shift that I showed you? He introduced, using
a CROP-seq approach, a lentiviral library
of the guide RNAs, differentiated them
to cardio myocytes, and then did single
cell RNA seq. Just in that atrioventricular canal myocardial
population, asked, do any of the guide RNAs make that pattern shift occur
to be more trisomy-like? Working with Sean Whalen
and Katie Pollard's lab, they set up a machine
learning algorithm that would call hits. Here, what I'm
showing you in red in this UMAP plot are
the disomic cells, blue are the trisomic, so they clearly
separate in space. The gray dots are each
of the guide RNAs. You can see most guide
RNAs don't do anything, which is what we'd expect. But some cause a shift closer
to the trisomic state, and we then took those and did secondary tasks
with them individually, not in a pool screen. To make a long story short, one of the guide RNAs virtually recapitulated
the pattern shift, and that turned out
to be a guide RNA activating a gene called HMGN1, which many of you will know is a nucleosome binding protein that functions often
as a co-activator, sometimes as a corepressor, at target sites, particularly of cell type specific
transcription factors. Hat I'm showing you here
again is that dot plot with the disomic control here, the trisomic all the
way on your right, and then in the
middle is activation just of HMGN1 with
the guide RNA, and you can see it largely
recapitulates the pattern. Particularly, these genes like TBX2 that I showed you
in R-spondin 3 that are normally high in the atrioventricular
canal myocardium are similarly down
regulated by HMGN1, like in the trisomic condition, and the chamber myocardial genes which are up-regulated in trisomy are also up-regulated
just with HMGN1. This suggests that
this one gene on chromosome 21 at least is
shifting the transcriptome, similar to what we
see in trisomy, with this identity shift, if you will, for the specialized myocardium
to be less specialized. That was encouraging.
But of course, what we want to know really is, in vivo, is this critical? We do have a way to test that, of course, because I told you, we have a mouse model,
and we have mice that are heterozygous for HMGN1. The simple experiment
is to cross the trisomic mouse with mice that are
heterozygous for HMGN1, and now you reduce the dose
of HMGN1 to two alleles, where everything else
has stayed the same. If this is the key gene
or one of the key genes, then we should rescue
the phenotype. We did that, and this
is the result we found, particularly for the more
serious cardiac defects, septal and
atrioventricular defects. You can see here
the trisomic mice, we get a very significant increase compared to wild type, and just by removing
one allele of HMGN1, we rescue this phenotype of
the cardiac defects in vivo. We believe this is
convincing evidence that HMGN1 is likely at least
one of the major genes. There has been very good
literature suggesting that a kinase DYRK1A is
another critical gene, and we're now trying to
test if both of these together could be sufficient. But as I mentioned, obviously, the key
question now is, where does HMGN bind
in these cells, and how does it affect
gene transcription? We're eagerly pursuing
those experiments in collaboration with
Vijay Ramani's laboratory, who has expertise in this area. But what we think is going on, even as we learn mechanism, is that the crux of this disease is likely a reprogramming
event, again, where this specialized
myocardium gets reprogrammed to be more like the ventricular myocardium
that it shouldn't be, and then that affects its
signals that it's sending to the endocardium to then affect the development
of the valves and the septa in this region. What I've tried to show
you today is how we can go from understanding the
developmental biology and molecular biology of
the system to being able to leverage that both for regenerative
medicine purposes and mechanistic understanding
of the genetics of human disease in ways that
will allow us to intervene. I tried to mention the brilliant trainees that have come through
the lab and worked on these projects
over the years. Many of them are listed here, including Sanjeev, and
great collaborators. This is my current laboratory, a fairly recent picture. With that, I'll close
and be happy to take any questions.
Thank you very much. Incredible work. It's really mind blowing. Anyway, I had two questions. One was about the last story. You showed RBFOX1 changes, and that is a regulator
of embryonic splicing. Have you looked
into alterations in splicing as an epitranscryptomic
instability that could actually lead to what's going on in the specification
of what should be atrioventricular tissue as opposed to myocardial
ventricular wall? Yeah, it's a great question, and we have worked on
splicing in other projects, and we're eager to
understand that it's hard to do with the
10x platform with single cell because
you don't get full transcriptomes to
understand splicing. There are some
computational approaches that try to do that, and we've been trying to collaborate with Lars
Steinmetz at Stanford, who's developed some of those, but we haven't succeeded. You can do the five prime
version, just saying. We can. Then the other question
is about anakinra. You're showing
IL-1 up-regulation and IL-1 Beta specifically. You can give anakinra, which is the IL-1
receptor that's exogenous that could
mop up that IL-1 Beta. Have you thought about that
in terms of preventing that myocardial reprogramming
towards a fibrotic state? We have. In fact, we have used
that and it was effective. There had been a
clinical trial of the IL-1 antibody
that had been done. It didn't get approval because of a number of side effects of blocking the immune
system more broadly. It led to greater
risk of infection. So that's why I think getting
with a greater degree of specificity that wouldn't
affect more broadly is key. But conceptually, that
I think showed us that this is the right
pathway to go after. Absolutely fantastic. I have three questions
about the Notch-1 work, but I promise they're short. They're all mostly
yes/no questions. For the Notch-1 reprogramming to a more osteoblastic
like state, that makes total sense. I'm curious whether there's
any explanation for perhaps the valve formation of a bicuspid format as
opposed to tricuspid. I'm not sure what you
thought about that. In the valve ex-plants
that you got from people who got the removal
or the swap surgery, was there any genomic
evidence for, say, somatic variance in
the Notch-1 pathway? Then, finally, I was
wondering when you tested the ERR-Alpha
blocking drug, whether or not there
were any adverse effects on the female mice. I'll try to be brief
in my answers as well. Sorry. For the first step, we
haven't been able to gain a lot of insight on the developmental
part of the anomaly, which is disappointing
to me because that's actually what I'm probably
most interested in. But our mice don't get bicuspid aortic valve
with this condition, so that's been a
rate limiting step. We don't fully
understand that part. For the second question
related to the? Somatic variance. Somatic variance. We
haven't looked at that, so I don't know if
that's the case, but it's a possibility
that there could be specific variation there. The third, we don't see sex
differences in those mice. I should say, which
I forgot to mention, that the vascular calcification
that occurs commonly in humans pathologically looks very similar to what we
see in the valve. When we do the clinical trial, we'll be looking at vascular
calcification also. We just don't know if it would work for that also
because there's not a good mouse model at all
for vascular calcification, but we have every
reason to think that it'll affect there also. Yes. Amazing talk. Really inspiring. I love the idea of
transforming fate in vivo, and that's happening
in the heart. We see it a lot in
epithelial tissue, so seeing it in the heart,
it's absolutely amazing. My question relates more on
lots of those changes that you've shown in those heat maps are actually niche factors, TGF Beta, WNT, VGFs. Maybe what are your
thoughts around this fate switch and how the
cells are actually undergoing this fate switch change
in their environment? You're absolutely right. What I didn't say is myocardial cells, we know a lot of the genes that are involved in valve formation, and they're dependent on
secreted factors like those that get sent and received by the
neighboring endocardium. Then the endocardium forms valves in these
acceptal regions. We do think that those are critical downstream
targets that are directly affected by the abnormality of that specialized myocardium. There are specialized
TGF Betas that are only secreted from
that valve myocardium, and there's special
TGF Beta receptors. They're only expressed in the endocardium
next to the valve, not in the endocardium
in the chambers. There's decades of
research on that, so we know the
pathways quite well. Exactly, you were spot on. Yes. Trisomy 21 has these
high incidence of these endocardio
cushion defect things. But I'm wondering,
since you seem like you maybe have one of
the main factors there, half the patients
with trisomy 21 don't have congenital
heart defects, but this would suggest they
have some predisposition. I'm wondering if
any work has been done in those that don't, just look at maybe gene
environment interactions or modifier genes that
might predispose to that more severe phenotype. It's a great point, and why is it that half
don't have disease? If you could figure that out, maybe there's a
prevention modality. There's actually been a lot
of effort, not by our lab, but by others in the field
to sequence large cohorts of people with trisomy 21
that have heart disease and those that don't to
look for modifier genes. It's been frustrating
for the field. So far, it hasn't been
obvious, there must be, but we haven't had
the power, I think, to identify that as yet.
It's a great point. Well, while we wait for
more questions in the room, we'll take one off of the Zoom. Given that you found
an association between telomere shortening
and aortic stenosis, does that give you any insight into aging related
diseases of the heart? Yeah, or period, aging related. When we had that finding, I immediately, of course, went to Liz Blackburn's office, which is on campus before
she'd come to San Diego briefly and went to share the data with her
and ask her for insights. I was surprised to learn that the field didn't have a good handle on why telomere shortening was
associated with aging, even though it's known to be. What I am actually very
excited about that we're pursuing right now is the idea that we actually
might have one of the best models that exist to figure out mechanism for telomere shortening
relationship to aging. One theory in the field is
that the telomeres loop back to contact promoters throughout the genome and
regulate transcription. The way to test that
experimentally, would be able to do Hi-C or three dimensional
conformation experiments in the setting of these
various mutations. The problem is, it's a
very small subset of cells in the valve
that are affected. You can't really figure
that out unless you can do single Hi-C and only recently has the technology
developed to do that. Longzhi Tan at Stanford is one who has developed some
of that technology. We're working with
his lab right now and have that single
cell Hi-C working. It looks like that's
exactly what we're seeing, and I think we might
be able to crack that, but we don't have the
answer right now. Dyskeratosis congenita, they
have mutations in TERC. Could you make an
IPS line out of that and do your
Hi-C experiment? Yes, that could be useful. What we have done just
in the last few weeks is a Hi-C experiment with the
mice that are null for TERC, and then mice that are null for TERC and
heterozygous for notch. I'll just share with you
the preliminary results, which I'm still
trying to understand, it turns out that in the
notch heterozygous setting, there's a decrease
in contacts and transcription of many of the genes that are
osteoblast-like. Then in the TERC knockout, that's true of TERC
knockout by itself. Then together, it's exaggerated. They seem to be hitting the same genes
even by themselves, and it's synergistic. Now we're still
trying to figure out. Is there a window of
opportunity after an infarct where you cannot do reprogramming in the heart? In other words, the
conversion from noncardiomyocytes
into a cardiomyocyte where nothing you
do will change. Yes, I think for a
variety of reasons, it wouldn't be done in the
acute setting immediately. Part of that is, if we were able to do it very efficiently, you want your fibroblast there to make scar and not
have a cardiac rupture. I actually don't
think we're at danger for that because we're
not so good at it. The efficiency is not
where we want it to be. The bigger reason
that won't be done is that for a clinical
trial purpose, there's so much variability
patient to patient in the acute setting of
where they'll end up. That clinical trials
become nearly impossible to see a
signal because there's so much variability from the time an injury occurs
to where that patient will land at their baseline after revascularization and
other medical therapies. You're just going to
get a ton of noise. I don't think you'd
ever see a signal. I think in clinical trials, it'll have to be once a
patient has stabilized, like we did in the pig. They've stabilized in whatever their decrement will be in
their cardiac function, so you have a reliable
change you can track. You define when it's too early, is there a point
where it's too late? We don't know that answer. It's hard to do really
chronic studies in animals to wait a long time and do it,
particularly in pigs. Honestly, we don't
know the answer. We'll have you be
the last question. I have one last question about the stability
of the reprogramming. You're showing one of
your first studies that you can reprogram fibroblasts to cardiomyocytes
in a scar tissue. How stable is this change? Whether they stay forever cardiomyocytes or
they can change fate. As Prince would say, forever is a mighty long time. But, what we do know, having studied the
epigenetics of this switch is that it's a wholesale epigenetic shift that appears to be very stable. In vivo and mice, when we've gone
several months out, it appears to be stable. We have every reason to
believe that after that, you've overcome that
epigenetic barrier and landed in a
different valley, let's say, using the Waddington
landscape as an example, that it would be an equally
difficult hurdle to get back. I think that's how
we think about it, but time will tell. We want to thank Deepac for just a really inspiring example of what we've often
talked about here, bedside to bench and
then back to the bedside and for just truly
illuminating. Thanks so much. Thank you. | ↗ |
| 28 | Dr. Yonatan Whitten | Stem Cell Therapy - Is It Worth It? My Treatment & Results | 303892 | 5067 | 915 | 67.7 | negative | 11:37 | In the last few years, regenerative medicine has become almost a household term, and the public really seems to have sunk their teeth into this new and very different approach to health care. One of the things that's most exciting for people is the prospect to regenerate diseased or damaged tissue. But there's also a ton of misinformation out there about things like stem cell therapy. And so in December of 2021, I flew down to Portoviar to myself to have stem cell therapy. In this video, I'm going to talk about what's involved in that procedure. I'm going to show footage from my treatment, and I'm going to talk about the results that I've gotten in the nine months since then. Let's get into this. Now, I've been fascinated by stem cell therapy ever since I first read about it. For me, it seemed like something straight out of a science fiction movie. But at the same time, I wasn't 100% sold on the whole thing. See, some of the clinics that offer stem cell therapy had made such wild claims and outrageous promises that it had kind of turned me off. But at the same time, I have this community of people that I work with, some of whom are in such severe pain and are just out of options that I felt like I owed it to them to find out if this was a viable treatment option that could help some people out. And so I decided to go have the procedure myself so that I could report back on my own findings. Now, in a personal note, I had had an old rotator cuff tear. I'm talking 16 years ago in my first year of clinical practice. I remember the moment I tore the muscle. I heard it tear. I felt the terrible ripping sensation in the shoulder. And I certainly remember the long process of rehabilitating it to regain functionality. I also had this nagging, right ankle injury. And I wasn't 100% sure what was causing it and why it was taking so long to get back to 100%. So I decided I would go down, have MRIs of both, see what they look like and find out if stem cell therapy would work for me. So how does the procedure itself work? Well, after filling out the booking form online, the dream body clinic pretty much takes care of everything. The only thing that you need to worry about is your transportation down to Port de Vierta. So in my case, the day after I arrived, I headed off to the dream body clinic first thing in the morning on an empty stomach. Now, the clinic itself is conveniently located inside of the largest hospital of the neighboring town of New Haven, Vierta. Now, the facility itself is state of the art and the location is, of course, gorgeous. So I had my blood drawn and then they transported me to the local imaging center where I had MRIs of my left shoulder and my right ankle. After that, I was done for the day. I could just go enjoy Mexico. A couple days later, I was back at the dream body clinic to review the findings of my MRIs with the doctors on staff. And sure enough, the MRI of the left shoulder showed evidence of that old injury, that tear in the super spinatus tendon, just a little tear and some inflammation surrounding it. And so I decided this was the perfect opportunity to see what stem cells could do for an old injury that had been fully rehabilitated. I'm talking, I have full range of motion in the joint and plenty of strength. I also decided to get a platelet-rich plasma injection and see what we could do for a shoulder that was already in pretty darn good shape. I'm talking zero pain. So let's see what it can do. I also decided to have an injection of 25 million stem cells into my right ankle after the MRI showed evidence of an old compression fracture that had not fully healed yet. And so I headed off to get another blood draw so that they would have plenty of platelets for that PRP injection. And then it was off to the treatment room for both injections. And like Josh, the owner of the dream body clinic said in my interview with him, the procedure itself was actually anticlimactic. The doctor was very professional, very quick. I felt zero pain in the injection and my left shoulder. In fact, I didn't even feel the need to go in. And in the right ankle, I felt just the slightest sensation of pressure inside the joint when the fluid went in and that feeling of pressure went away 15 to 20 minutes after getting up and walking around on the ankle. And so what happened immediately after the stem cell therapy? Well, not much to tell you the truth. I did exactly what dream body told me to do. I took three weeks of complete rest. And in that time, I didn't experience hardly anything. I had no pain, no inflammation or swelling, really no discomfort of any kind in either the shoulder or the ankle. I didn't need to take a single serving of the anti-inflammatory drug that they'd prescribed to keep me comfortable during that initial phase. And so I was really happy about that. And after that three weeks, I began slowly easing into the rehabilitation process, working on regaining full range of motion in my ankle and slowly building up strength in my left shoulder. And then right around the three-month mark, something really interesting happened. I genuinely couldn't remember at that point if I'd had my left ankle injected or my right ankle injected. I know that sounds strange, but I'd had a bad snowboarding injury that had affected my left ankle. And I really couldn't remember since they both now felt really good, which one was which, which was cool. Because it showed me that something was happening and what my new normal had become, where I'd just kind of expected to have some ache and stiffness in that right ankle that helped me to differentiate the two, was gone. So I had a new normal that didn't include those symptoms. So I was really happy about that. And the shoulder, it was building up strength. And then around the sixth month mark, I really noticed that my strength had taken off. Because I actually had to replace some gym equipment that could no longer challenge the left shoulder. I'd just become stronger than my gym equipment could accommodate. So I actually sold it off and got a new set of dumbbells and some extra weights that could accommodate the new level of strength. Now nine months later, I wouldn't believe it if I hadn't experienced it myself. My strength levels are back to what they were in my late 20s at the absolute peak of my strength. My jumping ability is through the roof and I'm super happy with the results of my procedure. Now just recently, a member of the Pain Fixed Protocol community posted on the Community Message Board about her results from stem cell therapy down at the dream body clinic. And you're talking about a woman who has been on the fire department, saving lives for 23 years, tons of wear and tear on both of her knees. You're talking about joints that were in really bad shape, almost to the point where she was denied treatment with stem cells because there almost wasn't enough tissue to even work with. But she posted about her results and I want you guys to hear from her what's possible with this amazing treatment. Because your problem had been going on so long and it'd be, and because it was tied to your job, you had imaging before and after your stem cell. Yeah. Yeah. You can talk about the change since January of 2022. So everybody knows we're recording this on October 1st, 2022. It was, I had just really jaw dropping. My right knee, which is not my bad knee, it's a healthy, it had a lot of osteoarthritis. So it was a solidly a stage four, but no traumatic damage in that joint. But that went from a four to a two. And that's what I mean, I'm reading my right knee results first. And when I saw that, I was like, I must be reading that wrong. And I actually looked up a few words. It was just, I was shocked. And it's like stage four, stage two. And so then I went to my left knee results, which is my bad knee, which had trauma. I actually had scoped and had cleaned up surgically after my injury in the fire department. And it said it went from a four to a two to three. Wow. So to read, you know, I like read it, I read it again. And all the things that they kind of called out in that original, where they were pointing at the type of cysts that were forming, they're just fluid filled sacs. There's like six things were called out on that first report for those verses and the bone cysts and the... A couple of the other things are going to be the appearance of the bone, right where it meets up with the highland cartilage. Another thing is going to be joint spacing, which is huge. And the other thing would have been the thickness of the highland cartilage that lines the joint. Had that actually measurably increased in your case? Yeah. And when they pulled those up, side to side, you know, like I'm sitting with the doctor then, he's like just pulling up the images and we're looking at kind of a before and after. And it was really... It was substantial. And I remember when we were looking at it, he's like, here, it's pretty thin, you know, like there's just the tiniest bit. He's like, and all I'm asking him back in January is, yeah, but will you inject it? He's like, yeah, I'll definitely inject it. But if it were any less, I wouldn't. And now we're looking at it, you know, last week and we're looking at it and he's going, we have plenty of work with here. And how is your prognosis, Denise, for being able to finish out your career and retire on your terms? Yeah. So I am just so happy report that I feel like I'm the master of my destiny again. Right now I don't feel 58. I feel like I'm 45, you know? And I'd like to get to 40 on my knees because that would give me the expectation of longevity to death, you know, like I would like to live the rest of my life without ever replacing my joints. That's such a good thing to say and a perfect way to round this off. Thanks so much for watching. I really hope that you enjoyed this video and that you'll put the information to good use if you want to find out more about stem cell therapy. Click the link in the upper left for an interview that I did with Josh Kettner, the owner of the dream body clinic. I'm also going to put the contact information for dream body in the description down below. They offer free consultation so you can find out for yourself if stem cell therapy is a good fit for you. Before you head out of here though, make sure to click that thumbs up button and subscribe to the channel so that you're updated every time a new video comes out. That's all for now. See you next week. | ↗ |
| 29 | The Royal Society of Victoria | Using Cellular Reprogramming & CRISPR Technologies to Regenerate the R... | 1057 | 38 | 3 | 67.7 | positive | 10:04 | Hello. Thank you for the opportunity to present my research. As you mentioned, I'm a PhD student from the University of Melbourne from the Center for Higher Research Australia. I'm also going to talk about the retina. The aim of a PhD is using cellular reprogramming to regenerate the retina and to treat brain loss. Let's begin. I'm also going to ask you a question. I want you to think about how would you feel if you had to face your everyday life with your vision looking like this or in complete blindness. Seems impossible, right? Unfortunately, this is what people living with photoreceptor generation have to face every day. Photoreceptors are cells that are key for our vision. They are located at the back of the retina and they are responsible for detecting the signals that are in the light and that our brain needs to form the images that we see as vision. That's why when we have diseases that damage the photoreceptors, it has a profound impact in the quality of our vision and it can often lead into blindness. We have two types of photoreceptors on rods that regulate the vision during night or in dark conditions and cones that regulate vision during daylight and the detection of color. I am particularly interested in cones because that is the type of vision that we use most of the time. In fact, that is the type of vision that we're using at the moment to look at all these amusing presentations, not amusing but entertaining presentations. As I said, when we have a disease that affects the photoreceptors, it can often well, it results in visual impairment and it can develop into blindness. Blindness is a huge or global problem because it creates a profound impact in the quality of life of a patient and it also has a huge burden on our societies because it creates problems like isolation, psychological problems, not to mention the burden, the financial burden that it places on our health system. The data of photoreceptors is a process that is irreversible and in most cases, there are no treatments to restore vision once the photoreceptors are dead. The current approaches to treat these diseases is just to help the patients manage the disease or just prepare them to live alive with visual impairment or blindness, which is not ideal. Popular examples of diseases caused by photoreceptor dead are H-related molecular degeneration or AMD, which affects almost 196 million of people in the world and retinaity speckmentosa that affects 1.5 million worldwide. Luckily, there is a light at the end of the tunnel and novel technologies like gene therapies are promising avenue to treat vision loss. In fact, there's a prominent example called Loxeterna, which is a gene therapy that uses viruses and that it has been approved in many parts of the world, including Australia. Loxeterna treats a very specific type of retinaity speckmentosa, so unfortunately, it is only applicable to a very small percentage of patients living with visual impairment. So that's why in my PhD, I want to develop a treatment that would be applicable for all patients living with visual impairment caused by photoreceptor dead. It is based in a technology called cellular reprogramming that was awarded the Nobel Prize in the 2012 and when I first heard about this technology, it was amazed because before we used to think that the identity of material cells was at a definitive state and it couldn't be changed. But now we know that we can take cells of a patient like, let's say, skin cells and reprogram them to become other tissues like neurons, heart muscle and even photoreceptors. But how do you reprogram a cell? The answer is in our DNA. So basically, all the information that we have that we need to make all the tissues of our body is already in our DNA and the difference is how the cells use this information. For instance, I am particularly interested in a cell type called Mule Glyia that is in the retina and I want to reprogram it into photoreceptors because they have more acute supportive role in the retina. They can also regenerate, so it doesn't matter if we lose some of them by transforming them into photoreceptors. And they have also been shown to have stem cell activity in other organisms. So going back to Mule Glyia, at DNA, they have unlocked in their DNA the genes that they require to make Mule Glyia. But for instance, the genes that they need that encode for the recipe to make photoreceptors are locked. But with another technology that we use in our laboratory called CRISPR activation, we are able to activate specific genes whenever we want. So with this, we can unlock the genes that encode the recipe for making photoreceptors and then we can promote these cells to become confoltoreceptors. So with this approach, I want to develop a treatment that would stimulate Mule Glyia into becoming new cones in a degenerated retina with a single injection with the aim of replenishing the lost photoreceptors and potentially treating vision loss. The main challenge of cellular reprogramming is knowing the genes that you need to make the cell that you want in this case photoreceptors. So I developed a tool in the laboratory that allows me to detect their reprogram Mule Glyia into cones because they turn red, as you can see here. I coupled this tool with a potent technology called CRISPR activation screen that basically allows me to search all the genes within the human DNA to predict possible candidates that could make photoreceptors. In my experiment, I detected 196 genes that could potentially make reprogram Mule Glyia into photoreceptors and I selected a few of them because of their importance in cone photoreceptor development. Next, I tested different combinations of these genes to try to find some that would be effective in reprogramming Mule Glyia into photoreceptors and overall I tested more than 100 combinations and I was indeed able to detect some combinations that could reprogram Mule Glyia into photoreceptors because they turn red as I explained before with the tool that I developed. We were also very happy to see that our new cone photoreceptors were functional because they could respond to light which is a key characteristic of the photoreceptors. Now that I knew which genes could potentially or I could use to make con photoreceptors, we proceeded to do some preclinical studies on a red model that has photoreceptor degeneration and visual impairment. So what we did was to put this cone reprogramming genes into viruses and we injected these viruses into the eye of the rats and four weeks after we analyzed the effect it had in our inhibition. So we were very happy to see that our treatment was able to induce or promote a functional improvement in these rats for parameters that measure photoreceptor activity or the activity of all those cells within the retina. Well this is very exciting because it means that we're getting closer to at some day developing a treatment that could improve visual function after you lose the photoreceptors. I would like to finish summarizing my talk because I know that there was a lot of information. So the aim of a PhD was to develop a cellular reprogramming protocol that could allow you to generate new human cone photoreceptors. And I also show you how the viral delivery of these cone reprogramming genes improved the visual function in a rodent model that has photoreceptor degeneration. So overall our results provide an important preclinical evidence for using cell reprogramming as a gene therapy to treat photoreceptor loss. I would like to thank the members of my laboratory, the cellular reprogramming unit and of course all our collaborators because without them this wouldn't be possible. Thank you. | ↗ |
| 30 | Jeffrey Peng MD | Stem Cell Therapy For Arthritis - The Truth You Need To Know | 90426 | 1328 | 272 | 67.5 | negative | 7:04 | imagine a future where a simple treatment could repair your damaged joints solve chronic pain and restore Mobility stem cell therapies promise just that for those suffering from arthritis yet among soaring expectations and bold claims there remains an essential lingering question does the actual effectiveness of these therapies match their groundbreaking potential today we're going to take a dive into the world of stem cell treatments for Osteo arthritis we'll discuss the science scrutinize the evidence and I'll give you my recommendations on whether this novel treatment is the Breakthrough we've been hoping for hey everyone Dr Jeff paying here stem cell therapies are a cuttingedge treatment and offer high hopes for those suffering from osteoarthritis however while there has been substantial media coverage and marketing efforts surrounding stem cell therapies they often highlight anecdotal success stories and while personal stories can be very compelling they can create a perception of Effectiveness that may not be fully supported by clinical evidence so let's briefly explore the three main types of stem cells used in osteoarthritis treatment first there's bone marrow aspirate concentrate or BAC for short BAC is obtained from bone marrow and is usually harvested from the patient's iliac crest in the pelvic bone next we have atopos stromovascular fraction also known as svf svf is derived from fat tissue and is harvested through lipo suction last there are stem cells from umbilical cord which are ethically sourced and processed for clinical use each stem cell treatment whether it's BAC SP SPF or umbilical cord derived shares a common goal they utilize mesen kyal stem cells and growth factors to potentially repair and regenerate damaged tissues like bone cartilage and connective tissue in addition these therapies also aim to reduce pain and inflammation through their anti-inflammatory and immunomodulatory effects so that's all in theory but what does the actual clinical evidence indicate while numerous case reports and some smaller studies suggest positive outcomes with stem cell therapies the overall evidence remains inconclusive this is why many experts who follow the orthobiologic space have been eagerly awaiting the results of this latest clinical trial the study investigated the three types of stem cells again that's bmac svf and umbilical cord tissue the researchers compared each of these three stem cell injections to corticosteroid injections and reported outcomes at one year the results showed that there was no difference in pain scores between any of these stem cell therapies when compared to cortisone injections in addition no treatment group saw any notable Improvement in MRI scores this suggests that none of these cellular treatments helped repair or regenerate anything within an arthritic knee now I want to reflect on these findings and emphasize a couple key points first this was a very well- conducted study with a large sample size of nearly 500 patients this is significantly more than the 20 to 30 patients in other clinical trials and therefore lends greater reliability to its findings second the study questions the effectiveness of stem cell treatments compared to corticosteroid injections for knee osteoarthritis this raises an important question is it worth paying thousands of dollars for a treatment not outright Superior to less expensive Alternatives now some critics would argue that a one-year study may not be sufficient to evaluate the long-term benefits or structural Improvement improvements that stem cell treatments could provide however it's important to note that individuals considering stem cell therapy often seek immediate results and may be reluctant to invest a significant amount of money in a treatment that requires several years to potentially show benefits for all these reasons I currently do not recommend stem cell therapy for the treatment of osteoarthritis this decision is based on the mixed results from recent clinical trials many of which show little to no benefit from these treatments furthermore the high cost of stem cell procedures represents a substantial Financial Risk especially considering the uncertainty of their effectiveness now a quick note on cortisone injections although the mentioned study showed no significant difference in Effectiveness between Cortisone and stem cell treatments this doesn't mean that everyone should be getting cortisone injection I've covered the risk of corticosteroid injections in a separate video which I'll link here for further details okay so what's a better alternative to cortisone or stem cells I recommend considering platelet rich plasma injections PRP has been proven highly effective in treating osteoarthritis and is considerably more affordable than stem cell treatments more importantly a wide range of studies including randomized control trials systematic reviews and meta analyses have shown that platelet rich plasma injections are more effective than Placebo cortisone injections and hyaluronic acid injections other Studies have even compared PRP injections to arthoscopic surgery and reported similar outcomes long-term studies suggest PRP injections can slow down the progression of arthritis and delay the need for knee replacement surgery in fact both the American Academy of orthopedic surgeons and the American Medical Society for sports medicine have acknowledged the effectiveness of PRP they've released summaries and consensus statements highlighting prp's significant benefits in reducing pain and enhancing joint function in knee osteoarthritis so for those considering orthobiologic therapies and regenerative medicine I generally recommend against stem cell injections they tend to be more expensive and inv Ive without necessarily offering better results instead I advocate for platelet rich plasma injections which I suggest to my patients as a more viable option lastly you need to know that not all PRP injections are the same there are many factors that influence the effectiveness of PRP and not paying attention to these can result in less favorable outcomes so check out this deep dive where I discuss the critical factors to consider and potential pitfalls to avoid during the treatment process | ↗ |
| 31 | TEDx Talks | The Promise of Stem Cell Therapy | Neil Neimark, MD | TEDxAshland | 121137 | 2169 | 234 | 67.4 | positive | 17:36 | let me start by asking you all a question how many of you here have ever injured yourself if you've ever fallen down and scraped the knee or twisted an ankle maybe strained your back or got a paper cut or a splinter or something like that please raise your hand now and keep it up for a moment great now all those of you who've healed from your injury please put your hand down now but if you're still suffering from a chronic old injury please keep your hand up for a moment great think you can all put your hands down now all those of you who've healed from a prior injury have experienced first hand the healing power of stem cells how because all tissue repair in the body is initiated by stem cells and in the words of dr. Harry Adel s'en and orthopedic stem cell specialists anytime you have healing after an injury it's a stem cell mediated event now those of you who are still suffering from a prior injury your pain or loss of function is due to the fact that either you do not have enough stem cells to fully heal the damaged area or the stem cells that you do have are simply not functioning optimally but here's the good news there are other areas of your body where you have plenty of stem cells that are functioning beautifully for example the bone marrow or your adipose tissue that's fat tissue does anybody here have a little extra fat they'd like to get rid of most of us do and if you take the stem cells from that fat where they are plentiful and you transplant them to an area of the body where they're in short supply then a tremendous amount of healing can occur and this is the essence of what we call regenerative medicine utilizing the body's own stem cells or stem cells from an outside source like the umbilical cord or and the otic tissue of a healthy baby delivery in order to stimulate tissue he and repair now as a family doctor for over 35 years I've seen the positive results of stem-cell therapy in my own practice and in reviews of the current literature and I truly believe that the next great advance in medical care will not be a magic pill it will be a miraculous cell called the MSC the mesenchymal stem cell and it will change the landscape of medicine as we know it over 30 years ago dr. Bernie Siegel the Yale author and surgeon used to say as a surgeon I cut into the body and I rely on it to heal I don't have to yell into the wound and tell it how he understood that the healing system lies within us what he didn't know at the time is that it is the MSC that mesenchymal stem cell that is the conductor of that healing system and it initiates and orchestrates the healing process now in this slide you can see the MS CS are the are the pink cells here lining the capillary bed and most remarkably the reason dr. Siegel never have the yell into a wound and tell it how to heal is because the MSC's yell into the wound for him they don't use regular words of course they use chemical words called signaling molecules and these are natural drug like compounds that stimulate tissue healing now whenever there's damage in the body these pink cells the MS CS go to the damaged area and they survey the area they begin to collect data and they communicate with the other cells in that area and then they intelligently respond by releasing a variety excuse me by releasing a variety of drug like molecules that initiate tissue healing and repair this is why dr. Arnold Kaplan who's a stem cell researcher at Case Western Reserve says that the MSC is an injuries cific drugstore because if you take an MSc and you put it in and damaged injured knee it will produce very different drug like molecules then if you take that same MSC and you put it in an inflamed lung or a damaged liver that's because MSC's are stem cells that are data-driven from the local information they're intelligently responsive to that information and their injuries specific drugstores now where do these drug stores exist in the human body well they exist in an area that we call the universal stem cell niche and that's where all tissue healing and repair occur now in order to explain this concept to you I had to create a fairly complex medical slide so be patient with me I promise I'll walk you through it slowly and even those of you who just don't get science will get it I promise so here it is the universal stem cell niche okay I'm kidding it's not a complex slide but I want to point out a couple of things the universal stem cell niche is simply the location it's the concert hall if you will where all the members of this healing system Philharmonic Orchestra play now leading the orchestra is the MSC who waves the baton and sends these signaling molecules to all the members of the orchestra to ensure that they play their parts that is they do the healing to the best of their ability now here in the front section we have the stringed instruments which are the progenitor cells these are called tissue-specific stem cells and every organ in the body has progenitor cells that only create cells unique to that organ so for example this bone progenitor cell only creates new bone cells and the heart progenitor cell only creates new heart cells and the same is true for every organ in the body now in the middle section where the woodwinds and brass are we have the vascular players these are the capillaries the red blood cells white blood cells and platelets that carry all the healing elements to the body and to the damaged tissue and lastly we have the peri sites this is the percussion section these parasites are those pink cells you saw in that electron micrograph and they have these little finger-like projections that go on to the capillary wall and they monitor they keep their finger on the pulse the rhythm the beat of the local scene and whenever there's damage they break off they go to the conductor's podium and they recruit a whole new healing system Orchestra to initiate tissue healing and repair now the universal stem cell niche is so vital to our well-being that in the words of dr. kristin Camela a leading stem cell scientist if you didn't have stem cells you could only live for about an hour now as amazing as that fact is even more amazing is the fact that these stem cells are helping real patients in real life medical situations get well one of my favorite quotes of all time comes from the American poet Muriel Rukeyser who said the universe is made of stories not of atoms so I want to tell you Jim W story Jim first came to me in August of last year complaining he needed a preoperative clearance for a left hip he needed a total hip replacement now he had been having a lot of pain a lot of clicking and he could no longer walk his dog honey so he was miserable now a year before he had had a total hip replacement in his right hip and that recovery was complicated by an infection and it took him over three months to heal and he was miserable during that time so when I mentioned to him the possibility of doing stem-cell therapy he was interested but he was a little skeptical because his doctor had told in his hip was bone-on-bone so he said only surgery is gonna work nevertheless he was willing to give it a try so under ultrasound guidance I injected about 8 million MSc stem cells into his left hip the whole procedure only took about 15 minutes it hurts no more than a blood draw basically and we put a bandaid on and Jim walked home and I said to him Jim be patient it takes about 3 to 4 months to see results well at the 3-month point I saw Jim and he was a little discouraged he was only about 25% better but I said to him Jim be patient let's give it a little longer so in February of this year at the six-month point I saw Jim again and he was ecstatic he was in virtually no pain he could barely tell the difference between the left hip and the right hip and most importantly he was able to take his dog honey out on 45-minute walks pain-free now Jim's a little camera-shy but I was able to catch this photo of him back on the happy trail with honey again now let me show you what happened inside Jim's hip when we put those stem cells in what happened is the stem cells go up to the conductor's podium they assess the area they assess the damage and then they send these signaling molecules to the progenitor cells to the tissue specific bone stem cells and cartilage stem cells that exist in that area and they've always existed in that area the problem is as we get older they decrease in number and then with wear and tear sometimes they get a little sleepy and tired and they get weak and weary and they lay down and take a nap so when we put those MSC's in they awaken Jim's napping progenitor stem cells they reenergize them and they come to life and they start creating new cartilage new bone new ligaments that lead to the growth and repair of that hip now stem cells don't only work in area in aging painful joints they also work in any can anytime in the body where there's excess inflammation immune system problems or wear and tear now this is a list of clinical trials being studied by dr. Neil Riordan an author and stem-cell researcher down in Panama all with very positive results and when you see this list of seemingly diverse conditions all responding well to MSC therapy everything from autism to asthma to osteoarthritis rheumatoid arthritis spinal cord injury you begin to appreciate the power of the MSC to awaken our healing system now I want to tell you one other example of how stem cells have helped patients with diabetes prevent pain and suffering in this study by dr. Prochazka at the University Hospital in Ostrava in the Czech Republic he studied 96 patients with what we call critical limb ischemia that's low blood flow to the feet and he divided these patients up into two groups now mind you all these patients were at risk for amputation because diabetics easily get in little cuts on the bottom of their feet that can get infected it can spread to the bone and often necessitate an amputation so in the first group the patients were given stem cells and these stem cells were taken from their bone marrow and they were injected along the leg here and along the foot ulcer base and in that group of patients 79 percent went on to heal completely by the 90 day point unfortunately 21 percent of those patients did require an amputation now in the group - that did not receive stem cells 44% of them required an amputation that's over twice as many patients needing an amputation they could have been entirely prevented by a single stem cell injection in a procedure that basically took an hour and a half to complete now I want to show you what happened beneath the sir or on the foot first with this critical limb ischemia you can see it they 0 this big wide gaping wound by day 30 it's a fraction of what it was in ninety days after a single stem cell injection it's almost completely healed now if you look beneath the surface at the blood flow what we have here is called an angiogram this is a picture of the blood vessels that go down to the feet on the left here this is the the foots down here and this is the top of the leg the calf you see what this is before stem cells it looks like a little country road or two barely carrying any blood down to the foot now ninety days after a single stem cell injection what you see here looks like a major metropolitan freeway system carrying massive amounts of blood down to the feet and remember the MSC not only heals tissue but it's also what we call angio genic it stimulates new blood vessel formation and because these MSC's like to live along the capillaries the more blood flow you have the more stem cells the more stem cells the better the healing the better your health I want to leave you with a quote from one of my personal heroes Norman Cousins who used to say the doctor has a role beyond the prescription pad to invoke the patient's own bodily resources for healing what this means is we need to just stop throwing a drug at every problem we need to learn how to harness the regenerative powers of our own healing system not only through advanced stem cell technologies but also through better nutrition better lifestyle choices better stress management and living a life of contribution purpose and mean but it's up to each and every one of us to get the word out about stem cells why because no drug company or surgical device company is gonna tell you about all the benefits of stem cell therapy because it disrupts their industry it eats into their market share and their profits so there's not going to be any fancy TV ads or print ads telling you all about the amazing benefits of stem cell therapy the task is ours it's up to us but if we rise up to that task this is what the future holds every patient with heart attack or stroke will immediately receive a series of MSC infusions that will help minimize scarring of the heart and limit the neurological damage and disability every child with autism will receive a series of MSC infusions that will help reverse the inflammation in their brain and help reintegrate that child into a healthy normal life and every patient with autoimmune disease whether it's diabetes lupus MS or rheumatoid will receive a series of MSC infusions that will help reset their immune system at the root cause level and help them to minimize their exposure to dangerous drugs and dangerous side effects there's an ancient teaching that says whoever saves a single life it's as if they saved the entire world so please share this information with just one loved one one co-worker one family member who may benefit from stem-cell therapy and together let's help save just one person's life let's help alleviate just one person suffering and let's help make a better healthier world through the promise and the proof of stem cell therapy thank you [Applause] | ↗ |
| 32 | Doctor Becker | "This Ancient Grain DOUBLES Stem Cell Repair & REVERSES Cellular Aging... | 4320 | 338 | 23 | 66.8 | positive | 31:24 | No transcript | ↗ |
| 33 | Peptide Science Institute | Longevity Experts Are Missing This About Aging (And It’s Costing You Y... | 540 | 44 | 4 | 66.4 | positive | 30:47 | No transcript | ↗ |
| 34 | Longevity Science News | Cellular reprogramming works | 4383 | 177 | 6 | 66.1 | positive | 0:28 | cellular reprogramming is one of the hottest topics in longevity science right now it's so hot right now in fact billions of dollars are flowing into this technology and companies like altto Labs reportedly backed by Jeff Bezos now a new pre-print study describes how using gene therapy to induce reprogramming can increase the lifespans of mice mice again I was hoping for humans but yeah mice keep | ↗ |
| 35 | Longevity Summit Dublin | Rejuvenation Through Cellular Reprogramming- Yuri Deigin at Longevity ... | 2615 | 84 | 5 | 65.8 | positive | 31:21 | the next um speaker Yuri Degen entrepreneur and biotech expert who is now all right here we go yeah who is now the CEO of um youth Biotherapeutics specializing on genetical programming tissue specific in Vivo thank you so much for being here thank you it's my pleasure I guess today I won't be talking about my company or pitching anything uh I'll just talk about some fundamental biology aging biology that uh I I'm fascinated by and I actually as I was introduced as a kind of reprogramming guy before I became a reprogramming guy I was a person very interested in germline Rejuvenation and it's germline Rejuvenation that ultimately drove me to reprogramming once reprogramming showed its great potential to rejuvenate cells essentially ameliorate all cellular homeworks and also in Vivo produce Rejuvenation and live extension but um to uh oh there we go to to dive into the processes that basically make the germline immortal uh I think it's it's very illiter illustrative for ourselves and for uh us as an aging field to see What mechanisms already exist in nature that produce Rejuvenation and germline being a prime example of these mechanisms because all of us here can trace our ancestry back three and a half billion years ago to our common ancestor and this is actually our all right there we go our genealogical tree dating back all the way back to three and a half billion years ago to our common ancestor and it's fascinating that all of us here have a unbreakable line of successful regenerating events to that point in time and so the the interesting question I think from a very early stage in the field of aging biology was what exactly happens to the germline to enable us to enable it to have this Rejuvenation and one of the first questions was maybe germline is somehow prevented from accumulating damage in the first place but I think then later on indications were that it's not exactly the case and there might be actual active mechanisms of damage clearance and by now basically this presentation is all about examples of such active mechanisms of damage clearance that hopefully we can repurpose for ourselves because in the case of the germline they're reserved for reproduction for sexual reproduction when genes decided it's beneficial to activate these mechanisms but for some reason they decided that in the context of an already formed adult organism these mechanisms need not apply but for ourselves we're very selfish we'd like to kind of hack our genes and and hack our biology to use these mechanisms to Keep Us Alive rather than successive generations and so today I'll show some examples of What mechanisms we have now learned we collectively as a field have now learned are responsible for Rejuvenation in germline cells and then what we can do to actually repurpose them for our ourselves in somatic cells in cells of an already formed organism and so as I said uh one of the questions early on was is there some sort of privileged uh do journalists are protected from Aging in the first place and the answer to that is no there is accumulated damage uh in germline cells as well and while there is some maybe some degree of this kind of protection from aging damage still accumulates in germline cells and in the context of mammals for example you know our egg cells are the same age as the mother because they get formed when the mother is still an embryo and they show a pattern of accumulated damage which after fertilization is actually actively cleared and so some examples from other organisms also show this highly conserved evolutionary mechanism of clearing damage when sexual reproduction takes place and there's also this this question that's been asked before are germline cells Protected Their evidence from experiments shown here kind of summarize here in the slides have shown that germline cells are actually not actively protected from accumulating this damage is already already mentioned and so today just want to show several examples from several species kind of progressively from the farthest away from us to the closest yeast farthest and the closest being the mice that there is this active mechanism of Rejuvenation in the germline cells so starting from yeast uh just want to highlight this work by Elton who used to work in the Angelic Ammons Lab at MIT unfortunately Angelica passed away several years ago now Elgin has her own lab in Berkeley and so these experiments were done by them together many years ago and so in yeast there's uh two sorts of lifespans there's chronological Iceland and replica replicative lifespan and so in yeast they notice that this active process of damage clearance only is reserved for sexual reproduction for gametogenesis or sporulation which induces gametogenesis and so this work is based upon this concept of replicative lifespan which gets reset by this gametogenesis process and so the key findings by unal and Ammon were that it is the sporulation process that is reserved for this sexual reproduction that induces reset not only reduces reset of replicative lifespan but also active Rejuvenation and clearance of damage that has been accumulated in the cell uh previously and of course yeast are a special case because they're a single cellular organisms which is kind of both the somatic cell and the gamete depending on the context and all the damage you can relating within the single cell has to be removed during the the sexual reproduction process to to induce this Rejuvenation event and so they Dove deep into the mechanisms of this damage clearance and they show that there is active clearance of carbonylight proteins Advanced glycation and products extra bosomal circles that are all examples of damage accumulating in yeast during kind of vegetative growth non-sexual reproduction and then if sporulation is induced if the sexual reproduction is induced then all of those examples of damage get cleared and yeast get essentially have reset their reproductive lifespan and this is their experimental design uh just very simply they tracked various yeast cells both old ones and young ones and then they induce sporulation in both old cells and young cells and then looked into whether they were able to reset lifespan whether there was any discernible difference between the old cell and the young cell after the sporulation event and weather damage was cleared by this sporulation event this gametogenesis induction of sexual reproduction and so these slides basically go into a little more detail on what I already said they've observed they've observed that sporulation resets live spending yeast this repetitive lifespan the old uh modern cells the red line normally have only on average five divisions left in their lifespan in in their experiment while young cells have about 18 medium number of cell divisions in the reperative lifespan but if sporulation is induced both old former old and young yeast cells have a new kind of lease on life new counter of 18 cell divisions before they die and so this has shown that sporulation does reset replicative lifespan in yeast and then also they looked into the damage that gets accumulated during the lifetime of yeast cells and they also demonstrated that it is actively cleared carbonylated proteins which is a form of damage they showed that it's during Vegeta vegetative growth non-sexual growth they get accumulated but after sporulation after sexual reproduction they are fully cleared and this is just another slide with more information on on their procedure where they track down different aspects of these carbonylated proteins just basically to show that they have robust data for for the claims that they're making that carbonyl proteins are fully cleared by the gametogenesis process also another aspect of Aging Hallmark of Aging in yeast are these extra ribosomal Circles of uh our DNA which get kind of accumulated in in the cell and basically are a homework of Aging after fertilization uh sorry after gametogenesis these are DNA circles are expunged and nuclear nuclearly morphology is normalized by again the gametogenesis process so this is another example of damage that gets actively cleared by this correlation process and while an Old Mother cell might exhibit many of these extra ribosomal circles uh after extra chromosomal circuits sorry ribosomal extra chromosomal circles after sporulation event these circles are cleared and then they dove into what exactly is needed in terms of the mechanism to enable this Rejuvenation they were asking is it meiosis that is responsible for Rejuvenation that we observe in east or maybe it's you know dilution during meiosis because normally a Mother cell gets divided into four daughter tetrads during speculation maybe there's some sort of dilution that happens from one Mother cell that partitions the damage into the four daughter cells but uh in in a nutshell the answer they arrive to is no meiosis is not the deciding factor it's not the replication of DNA sorry it's not the division of the cell into four tetrads and the dilution of damage that is responsible for the gametogenesis process for the clearance of damage associated with the gametogenesis process and so they've tracked the levels of damage during the meiosis process as shown here and they they show that until kind of the final stage of sporulation even when you have the tetrad already formed for different daughter cells you still have high levels of these carbonylated proteins as an example which get cleared only after in the final stages of the the sporulation moreover if you actually disable meiosis which you can do in in these cells there's some strains where you can either in this example instead of the four daughter cells instead of two division two successive divisions you get only one division so you get two daughter cells in this case it's still uh cells get fully rejuvenated they in terms of reproductive lifespan they still get restored to full potential and finally even if you fully disable meiosis basically if you maintain the same cell the same single cell as the mother cell ends up being the daughter cell so there's nothing to dilute I mean there's no dilution because all the damage stays within the same cell even in that case use observe Rejuvenation clearance of damage and reset of replicative lifespan so all together that shows that biosis itself the process of meiosis crossing over or doubling of the DNA is not what restores the morphology and the uh of say our DNA circles and clears the damage so it could be connected to meiosis meiosis might be inducing this kind of system of Rejuvenation that triggers all of this clearance of damage but meiosis itself the the divisions that happens during meiosis DNA divisions is not what causes the the damage to be cleared and they conclude with the dilution not being the key factor driving the Rejuvenation of yeast cells during sexual reproduction basically what they observed in in their work argues against dilution but for active damage clearance mechanisms in yeast during sexual reproduction and this is actually what we see time and time again time and time again in other species other animals other examples during sexual reproduction of active damage clearance and the best example I mean the closest example to ourselves to to mammals like us are mice and in mice something quite similar was observed by Maryland several years ago where she studied exactly the same process of uh sexual reproduction and damage clearance in germline cells in you know fertilized eggs that happens as part of the sexual reproduction in in these organisms and basically she demonstrated that during early embryogenesis just after fertilization in the several days after use have active clearance of damage again carbonylated proteins Advanced glycation and products and Etc in Mouse egg cells which is very close to you know our embryogenesis as well mammalian embryogenesis so it's essentially I would say guarantee that we have the same process in human cells happening during human embryogenous active clearance of damage and she narrowed it down to this 20 subunit of the Proto so I'm showing that it's the protosomal mechanisms that are responsible for clearance of damage during mouse embryogenesis that clear that damage and she had very good methodology showing the accumulated damage in mirin all sides and after visualization showing where the damage gets localized and actual clearance of the damage and she showed that for example carbonylate proteins accumulate just outside of the nucleus and within the cytoplasm of of the fertilized egg and then she followed it through the process of embryogenesis and cell divisions that happens during marine embryogenesis and show that over time several days after fertilization levels of damage in for example here carbonylated proteins next slide ages get drops within days to much much lower levels essentially to to zero during the active process of damage clearance and also she visualized that this damage actually uh doesn't damage clearance doesn't happen immediately but it starts happening when there's active differentiation of embryonic stem cells in in a blastocyst and the the if the damage is actually localized in the Inner Cell Mass that's shown here I wish I had a pointer on this slide and basically she was able to track it down during the embryogenesis process and and showing that this damage gets cleared over time and she asked a very good question basically why is it that aged tissues accumulate this damage and actually she showed that in in the embryonic stem cells before the active process of damage clearance the level of this damage is is similar to to like the liver and the brain of old or not old sex six months old mice you know adult mice but yet they're fully cleared during the emergence process in in germline cells but why not in somatic tissues so this kind of question that I think we're all asking why do genes decide to reserve this process only for sexual reproduction but not for keeping us healthier for longer uh so I think you know we we don't really need to answer that question as long as we can actually use these Pros processes you use the mechanisms of damage clearance that are already present in the genes of our organism and maybe just activating those genes in the somatic cells and this actually ties back into partial reporgan where I think partially programming activates some of these mechanisms and some of these Pathways to actually actively clear the damage and so the conclusions of her numbering listed here basically uh show that there's active Rejuvenation happening after fertilization in germline cells and the key active mechanism that she narrowed down was protosomal degradation of carbonylated proteins and AGS in addition to of course there's many other things that happen during embryogenesis complete reset of the epigenetic landscape methylation landscape Etc but she didn't she didn't focus on that she focused on actual damage protein accumulated damage in murine cells and speaking of carbonyl proteins and protosomes there were examples in other species showing very similar mechanisms clearance of carbonylated proteins and there is kind of two schools of thought one thing so it's the protosome other things it's the lysosome that plays the key role and as I mentioned Moline hernabring thought it's the protosome or had data showing it's a protosome and other groups for example in drosophila showed also that the protosome plays a key role this is a very cool experiment that they did they showed a particular uh subunit 26 subunit of the protosome was critical for lifespan of drosophila if you down regulate this subunit flies live for much shorter time period if you upregulated this actually extends lifespan of drosophila and so the authors concluded that you know solar degradation of carbonylated proteins and other misfolded proteins is a key mechanism for Rejuvenation in inrosophil including germline Rejuvenation and they were able to kind of repurpose it for somatic Rejuvenation and extending lifespan in the Flies also another group showed in nematodes also that it seems to be the protosome playing a key role in clearing damage Journal energy during General Rejuvenation in nematodes whereas another group and I have a few slides after show that as it's actually lysosome so there's kind of again two schools of thought but I think it would be good to upregulate both lysosomal and proteosomal mechanic in somatic cells and you know enjoy the Machinery of Rejuvenation in our somatic cells and finally on nematodes there there was a very interesting paper that showed very nice visualization that the germline cells the egg cells in nematodes actually have higher levels of damage than surrounding kind of somatic tissues so again it's not that the germline cells are somehow privileged from accumulated damage on the contrary here you see that at least in the levels of kind of oxidized levels of oxidation and oxidized proteins they're higher than surrounding tissues and yet when it it's time for them to get fertilized they're actively cleared of that damage and you know this is the actual Machinery that helps them enjoy Rejuvenation rather than a process of prevention of accumulation of this damage and so this is the work in nematodes that I mentioned by Cynthia Canyon's group and Adam Bonner in in her group that showed that in nematodes they studied in in deep detail what exactly happens during nematodes and they showed that in nematodes it's actually just before fertilization that this active clearance of damage happens because nematodes they sell fertilize they actually know when the fertilization event is going to occur and so just before that they start clearing the damage of their egg cells and the major kind of pathway there is the signaling pathway uses the major sperm proteins that kind of induce this rejuvenating event and induce this Machinery to clear the damage in in their in their egg cells and so yeah basically the next two slides summarize these findings showing that nematodes can clear the damage in in their egg cells on demand when they know that they're going to be fertilized they activate this clearance machinery and so it's the major sperm proteins that play the key role and if they mimic just the signaling they also can prevent aggregation of uh this this damage in their all sides and as I mentioned when they when they Dove deep into the mechanisms of this damage clearance the group of atom Bonner and Cynthia Kenyan they show that it's the lysosome that plays The Cure rather than protosome and they they the way they kind of were able to conclude this they knocked down or knocked out several key mechanisms of lysosomal degradation and were able to show that one of the subunits the V8 of v80pas lysosomal proton pump is important for this damage clearance and if actually they disable or knock down the subunit that you get much worse damage clearance so they were they concluded that lysosomal degradation it plays a key role here in in nematodes and to kind of bolster their conclusions there's some data from frogs that also argues that it's actually the lysosome that plays a cure role but as I said between lysosomal upregulation of lysosomes and protosomes it could probably would be good to upregulate both to uh be able to clear the damage in somatic cells but here in in frog oocytes they were showing that it's the lysosome that can that there's active clearance of damage in frog cells and it's the lysosome that plays a key role there now to try to tie it back to reprogramming as I mentioned that's what led me to believe reprogramming is repurposing some of the mechanisms of this germline rejuvenation uh there is great data from the Vadim gladyshev group and I know he's here in the in in the audience somewhere showing that epigenetic age is also not immediately reduced during the embryogenesis process but actually reaches immuno a minimum just before gastrulation or at gastrulation uh so this I think uh dovetails well with the observations of Malin herrenberg that show that again damage is not cleared immediately after fertilization but it's a gradual process that reaches a minimum I think eight days in mice that were in malin's results and here in vadim's result in vadim's groups results they also find the minimum around like eight to ten days during miles embryogenesis and as as we all know reprogramming has been shown to ameliorate all cellular hormone Hallmarks of aging on in a single cell and including clearance of damage and misfolded proteins Etc and so to me uh kind of the natural question because reprogramming already recapitulates a lot of this embryogenesis biology because essentially we're introducing the factors that are responsible for maintaining stemness and embryonic stem cells when we introduce those factors into somatic cell that somatic cell essentially kind of recapitulates the or moves back on the epigenetic lens came all the way landscape all the way back to embryonic state so it's to me very possible that the mechanisms that enable this clearance of damage are also the same mechanisms that are activated during the embryogenesis process and embryonic stem cells as was shown by million bring in in mice and in addition to the physiological Rejuvenation that we see during reprogramming we know that even partial reprogramming but can restore more youthful levels of gene expression as two papers this one showed and this one showed that partially programming restores a more youthful pattern of gene expression a more useful transcript transcriptome but more importantly on the physiological level just partially programming just kind of the beginning stages of reprogramming induce this Rejuvenation in the cells that reprogramming targets and so to me this all kind of ties back again into what exactly are reprogramming factors or yamanaka factors and of course we know that these factors are responsible for supporting stemness maintaining stemness on in embryonic stem cells and uh and of course they're also a Pioneer transcription factors they're able to access condensed chromatin open it up and induce gene expression of previously suppressed genes and transcription factors triggering kind of a Cascade of uh you know other transcription factors but also another aspect of human Aqua factors is that October OCT 4 and sox2 are also the factors that trigger this maternal to zygotic transition during early embryogenesis in mammals and this kind of falls in the same time period as this observation of epigenetic age reaching a minimum during gastrulation which kind of tying it all back together to me seems to imply that there could be some sub-programs that induce active damage clearance induce Rejuvenation and not just transcriptomic epigenetic but actual physiological Rejuvenation and clearing carbonylated proteins Etc that get activated during the early stages of reprogramming even partial reprogramming and this could be responsible for the observations that we see the partial reprogramming and we have these These are empirical observations that partial reprogramming just partial reprogramming can produce rejuvenating effects on on cells and so uh yeah I think this is a great quote regarding guest relation that it's the most important period in our life I think the observation that our epigenetic rage reaches minimal gastrulation and that we're rejuvenated during gastrulation plays back uh well to this quote so uh to conclude uh I think hopefully you know in this kind of quick Whirlwind tour of Decades of research into germline Rejuvenation I was able to at least kind of interest you in diving deeper into this topic and trying to figure out what exactly are the mechanisms that nature already has that maybe we can recapitulate and of course to me personally I think partial reprogramming is one such mechanisms it's far from ideal but or at least where you have it and that's why I think we should try to translate it as quickly as possible where some people should try to translate it as quickly as possible but other people fundamental resources should dig deeper into the mechanisms of that induced Rejuvenation germline cells and figure out how we can kind of apply them in the context of an already foreign organism and be able to kind of get control back from from our genes and control of our biology so with that thank you very much if you have any questions I would love to answer them [Applause] thank you so much maybe we have time yes for one or two questions before we go to our short break is there a mic around yeah it's coming here we have a question maybe you can raise your hand so it's easier for them to find you thanks so much thank you always fascinating um at the moment what is as far as you know the difference between Rejuvenation with the yamalaka factors in the best case situation and Rejuvenation by Nature you know uh yeah from the Native the cells who are going to give another animal yes thanks DJ I think it's a it's a great question because yeah obviously with the yemenak factors I mean we can fully rejuvenate a cell in a Petri dish and you know create a colony of fully rejuvenated cells with that if we redifferentiated back into original tissues have fully restored the functions a mitochondrial function that's a great example of uh fibroblasts from 100 year old donors that have suppressed mitochondrial function but if you reprogram them into prepotent stem cells and then back into fibroblasts they're like young like young fibroblasts with fully restored mitochondrial function so on a cellular level reprogramming can do this the problem is you can't do full reprogramming on you know in Vivo in the context of adult organisms because you can't afford to lose cell identity so definitely partial reprogramming is not there yet but on on you know full reprogramming I think it's already recapitulating a lot of urination that you know Nature has reserved for for journaling cells hopefully that that kind of answers the question uh well in terms of Hallmarks of Aging I don't think so because as it can slide summarized on cellular Hallmarks of Aging full reprogramming ameliorates all the cellulose homework solution of course there's you know extracellular Hallmarks of Aging there's a matrix and all of the other problems with signaling for example that is not even you know captured by by single cell reprogramming and so and of course the during reproduction it doesn't really care about the extracellular matrix it's something that could be another aspect why I chose to do that I can just build a whole new Matrix from scratch so there's still definitely ways to to for us to explore other ways of Rejuvenation in the in other contexts and clearance of damage in in other contexts any other questions I guess not thank you so much Yuri once again um great talk [Applause] | ↗ |
| 36 | Be Optimal | "Try It Now" - Most Effective Way To REGROW Mitochondria & REVERSE AGI... | 2453 | 41 | 9 | 65.5 | negative | 12:51 | All of these people were kind of couch potatoes, sedentary. They did not exercise a lot. Guess what? You're a f***ing idiot. Gurs, their walk in endurance improved by 60 meters. The researchers actually gave mine a peer to older people who took the uralithin A, a supplement every day for four months, or placebo. And these are people who were just average physical shape and endurance. The researchers measured their mitochondrial function at the beginning. Not so. And after four months, guess what they found. The people who took the uralithin A supplement, the mine a peer had better endurance. They had more energy generated by their muscles. Their mitochondrial function was better in blood tests. And then they actually biopsied their muscle. That's a pretty serious clinical trial. Meet William W. Lee, a Harvard trained physician, medical researcher, and best-selling author, who studies how the body protects and heals itself. He is also the president of the Angiogenesis Foundation. In his books, Eat to Beat Disease and Eat to Beat Your Diet, he explains that the right foods can help protect cells, support mitochondria, the body's energy producers, and improve overall health. His main message is simple. The foods we eat every day can help our bodies stay stronger, healthier, and more energetic. Why your mitochondria are dying? Aging does not mean that you have to decline. I'm gonna start by talking about something called mitochondria. You may have heard about mitochondria already. And if you haven't, I wanna tell you, these are little engines that are inside your cells and their powerhouses, all right? They're like batteries inside yourself. They generate all the energy that your cell needs, that your body relies on in order to be able to move. And to run all the processes in your body, all right? And when the mitochondria are fresh, just like a fresh battery, they can hold and deliver a lot of energy. But as you get older, just like an older battery, all right, those batteries can wear down, they can lose a lot of their power, right? Like an old battery's in a flashlight, right? The light isn't so bright anymore. And your energy can start to fade in your body as your mitochondria get older. When old mitochondrial that are not working that well start to pile up, well, guess what? Your body has a hard time actually generating the energy. This decline in mitochondrial health, we're starting to realize is one of the underlying causes of fatigue and muscle weakness. And actually it may wind up being behind underlying a growing number of age-related diseases. To understand why this supplement is getting so much attention, we first need to understand the real problem. The mitochondrial dysfunction. Think of mitochondria as the tiny batteries inside your cells. When those batteries are new and healthy, everything runs smoothly. Your body produces plenty of energy, your muscles feel strong, and your brain stays sharp. But as the years go by, those cellular batteries begin to wear out, just like an old phone battery that no longer holds a charge, aging mitochondria become weaker and less efficient. Your cells can't produce energy the way they used to. When this happens, you may start to notice symptoms such as muscle weakness and loss of strength, brain fog and difficulty concentrating, low energy and reduced stamina, visible signs of aging, including wrinkles and sagging skin. For a long time, scientists believe this decline was simply a normal part of getting older, something we had to accept. But research over the past few decades has revealed something fascinating. Your body actually has a built-in repair system designed to deal with damaged mitochondria. This process is called mitophagy. Mitophagy acts like a cellular cleanup crew, identifying worn-out mitochondria, breaking them down and clearing them away so your cells can replace them with new, healthier ones. And when this process works properly, it can help restore cellular energy, support healthier aging, and keep your body functioning more efficiently. Your body can make a natural substance, it's called uralithin A, that can help charge your batteries up, it can help your mitochondria perform better. And the way it does it is by cleaning up all the old, broken down, worn out, not so good mitochondria, right? So it's like taking all those old batteries out of your flashlight and tossing them out and adding new ones back in. Human studies. But it turns out human studies have looked at this and researchers at the Amizentis and Swiss Federal Institute of Technology in Switzerland, they did a clinical trial. In fact, they did a randomized placebo-controlled clinical trial by looking at 66 healthy adults said in Terry. So people were not moving around a lot, these are not athletes, okay? Couch potato, let's call it, and they were between the ages of 40 and 64, right in that middle age range, and they asked, what is the effect if you gave these couch potatoes between the ages of 40 and 64, some uralithin A, their body makes it by itself, but what if we gave them the uralithin A to charge them up? So what they did, they gave half of the subjects, uralithin A as an oral supplement, and they gave the other half of people a placebo, they did every day for four months, all right, and the results, striking in the group that got the uralithin A, okay? And remember, I told you the body makes it by itself, but in this case, they gave supplements to actually boost the uralithin A, guess what? People taking uralithin A, their muscle strength, increased by 12%, while as placebo group, no change in muscle strength at all. They got 12% extra muscle strength just by taking the uralithin A supplement. The other thing they did is they actually found the people who were taking the uralithin A had better walking endurance, right? So think about it, you're going for a walk on a long side walk, okay? More hike, or eventually you're gonna get tired. Well, walking endurance is how far you can go, and it turns out that people who took the uralithin A, and remember, all of these people were kind of couch potato, sedentary. They did not exercise a lot. Guess what? Uralithin A takers, if they're walking endurance, improved by 60 meters. Now you might say, what does that mean? I can't picture 60 meters. Well, imagine a 20 story building, 20 story side, tipped on its side, and walking the length of that building. That's how much more endurance, the people with uralithin A supplement actually had, and that makes total sense. If you take uralithin A, it helps to clear out all the old junky batteries, so that new batteries can be put in to the body. Guess what? You're gonna have fresh batteries. The star supplement, uralithin A, midopure. So the other thing is, I told you, not everyone's gut bacteria work the same way. Some people are not good metabolizers of a lager tanis, and that's where you can actually get benefit from taking a uralithin A supplement. There's one called midopure. If you want more energy, it might be a good idea to take it at any how, and it's been studied in human studies and shown to boost mitochondrial function like the way that I told you about earlier. But this is what you want from a supplement. You want to know that it actually works in clinical trials for actually done. So one of the trials, researchers actually gave my appear to older people who took the uralithin A supplement every day for four months or placebo, and these are people who were just average physical shape and endurance. The researchers measured their mitochondrial function at the beginning, not so good. So they were like suboptimal mitochondrial function. These people were not feeling particularly energetic. They, you know, they were a little fatigued before they started to study. Then they gave them the uralithin A might appear, and after four months, guess what they found. The people who took the uralithin A supplement, they might appear had better endurance. They had more energy generated by their muscles. Their mitochondrial function was better in blood tests, and then they actually biopsy their muscle. That's a pretty serious clinical trial, all right? And when they biopsy their muscle, guess what they found? They found that the gene expression, in other words, at the cellular level, that the people who took the uralithin A, they had more mitochondrial genes that were activated as well. That's pretty definitive, all right? And by the way, the uralithin A stimulated in mitochondria worked even better if you combine the supplement with exercise. Exercise stimulates your mitochondria as well, all right? So, clinical trials works well. It's pretty amazing, I think, for activating your mitochondria. The compound that has scientists, including researchers like William Lee, particularly excited, is called uralithin A. But here's something interesting, you usually don't get uralithin A directly from food. Instead, it's what scientists call a postbiotic. That means it's created inside your body when certain gut bacteria break down natural compounds found in foods such as pomegranates, walnuts, and berries. In other words, these foods provide the raw materials and your gut microbes convert them into uralithin A. However, there's a catch. Research suggests that more than 60% of people don't have enough of the specific gut bacteria needed to produce uralithin A efficiently. So even if someone eats pomegranates or berries regularly, their body may produce very little of this compound. That's one reason scientists became interested in a supplement form known as midopure. By delivering uralithin A directly, it bypasses the need for those specific gut bacteria and ensures the body receives the compound in a form that has been clinically studied for supporting mitochondrial health. A people who took uralithin A supplement, okay, which clears away all the junk and leaves room for pneumaticondria, their oxygen efficiency, their VO2 max, rose by 7% as well. When they looked at mitochondrial health, how healthy were the mitochondria? Uralithin A takers actually had 22% increase in the health of the mitochondria. Makes sense, right? Out with the old, in with the new 22% healthier. And then the research has measured something called isocarnitine, all right? Now isocarnitine is a marker of how the body burns fat for energy, all right? And guess what? The isocarnitine levels dropped by 14%. All right? So uralithin A takers had more efficient ways of using their fat. They didn't naturally need to actually burn fat by, you know, pedal to the metal. They could actually take it easy and still have efficient fat metabolism. And that's because they had better mitochondrial function. And then finally, the researchers looked at a blood marker called C reactor protein, all right? CRP, you might have heard about CRP, it's something that your functional doctor should be measuring. It's a measure, it's a, it reflects how much inflammation your, is your body? Uralithin A takers, guess what? Their CRP levels dropped by 16%. All right? That means that uralithin A is also anti-inflammatory as well. That's really interesting, right? Well, and the reason I'm telling you is because I was skeptical about uralithin A supplements that might have congrier for a long time. But I'm a scientist and really a good scientist always starts with having an open mind. So you might be skeptical about something, but let's look at the data. And I just show you the data. Uralithin A actually improves human parameters that you can measure that reflect better mitochondria and less inflammation. Just a quick, friendly note. This video is for educational and informational purposes only. It's based on scientific research and expert insights, but it's not medical advice. Everyone's body is different. So always talk with your doctor or a qualified healthcare professional before making changes to your diet. Supplements or health routine. | ↗ |
| 37 | Be Optimal | "Try It For 1 Day" - Most Effective Way To REGROW Stem Cells & Longev... | 128686 | 2047 | 81 | 65.4 | neutral | 14:38 | Humans regenerate using stem cells that come from the womb. So when we were developing in the womb, we were only stem cells. When we were born, we had extra stem cells. Did you know that the drinks you choose can actually boost your stem cells and help you live longer? Curious to find out which ones? Stick around. Because in this video, we're revealing the top three drinks that can supercharge your body's natural healing powers. Thanks to the groundbreaking research of Dr. William Lee. Trust me, you won't want to miss this. Meet Dr. William Lee, a world-renowned medical doctor and researcher with Harvard training. Dr. Lee is also a New York Times best-selling author, celebrated for his book E2B disease. Recently, he released another insightful book titled E2B your diet. Number one, hot chocolate. Dark chocolate. But I will tell you that cacao has been shown to actually double the number of stem cells flowing in your bloodstream just by having two cups of hot chocolate made with 80% high flavonal chocolate. Yeah, that's been done in people six years old with heart disease. The polyphenols in this dark chocolate that we know what they are. They're called pro-anthocyanidine. So I'm assigned to so, my job is actually know what are inside chemicals actually are. These are natural chemicals, all right? Most people don't need to know that, but you drink it and it tastes good. That's all you need to know. But I'll tell you, these natural chemicals found in cacao actually trigger a reaction in your body so that they call out the stem cells. So it is literally like bees flying out of a hive. Can double the number of stem cells and what's the practical impact? Well, there was a study done at UCSF in San Francisco that looked at 60-year-old men with heart disease. So these are people whose blood vessels were already not doing so well and their blood flow wasn't going so well either and their blood vessels were kind of sick. That's kind of the definition of heart disease. By having the stem cells coming out, they were able to actually double the resiliency, the function of their blood vessels. So they got better rebound, the better agility, their blood vessels are in better shape because their stem cells are regenerating their circulation. Wow. So this is human studies, right? Like most of the time you hear about scientists talking about rats or mice or cells, I'm talking about human studies. And that's kind of where we are with food is medicine. Many people think of chocolate as just a sweet treat, but real dark chocolate made from cacao actually contains powerful natural compounds called flavanols that can support your health in surprising ways. Flavanols are plant nutrients found in cacao beans. These compounds help your body in several important ways. First, they improve blood flow. Flavanols help your blood vessels relax and widen allowing oxygen and nutrients to move more easily throughout your body. Better circulation supports heart health, brain function and overall energy levels. Second, flavanols help reduce inflammation. Chronic inflammation is linked to many modern health problems, including heart disease, diabetes and aging related conditions. By calming inflammation, dark chocolate may help protect your body over time. Scientists have also discovered that cacao flavanols may support the body's natural repair system, including stem cells. Stem cells act like your body's internal repair crew, helping replace damaged or aging cells with new, healthy ones. Some studies suggest that regularly consuming high flavanol cacao can increase circulating stem cells, which may support healing and regeneration. Dark chocolate is also rich in antioxidants. These compounds protect your cells from oxidative stress, a process caused by free radicals that can damage cells and accelerate aging. This means that a warm cup of hot chocolate made with real, high cacao chocolate isn't just comforting. It can also support heart health, brain performance and long-term wellness when enjoyed in moderation. The key is choosing dark chocolate with high cacao content, 70% or more and limiting added sugar. So, when made the right way, hot chocolate becomes more than a dessert, it becomes a small daily habit that nourishes both body and mind. How to make hot chocolate healthier? Hot chocolate can be more than just a sweet comfort drink. It can also be a healthy choice if you prepare it the right way. To get the most health benefits, start by choosing unsweetened cocoa powder or a dark chocolate bar that contains at least 70-73% cacao. The higher the cacao content, the more beneficial plant compounds and antioxidants your drink will contain. Instead of using sugary mixes, prepare your hot chocolate with hot water or unsweetened almond milk. Almond milk adds a smooth, creamy texture while keeping the drink light and lower in calories. This helps you enjoy the richness of chocolate without excess sugar or fat. Many traditional hot chocolates include whipped cream and added sugar, but these extras can reduce the health benefits by adding unnecessary calories. Skipping them allows you to enjoy chocolate in a more balanced and nourishing way. If you still want extra flavor, you can enhance your drink naturally. A pinch of cinnamon adds warmth and may help support blood sugar balance, while a few drops of vanilla extract give natural sweetness without added sugar. These small additions make the drink taste indulgent while still supporting your health goals. In simple terms, a healthier hot chocolate is about keeping it simple and natural. Choose real cacao, avoid excess sugar, use healthier liquids, add natural flavors instead of sugary toppings. Prepare this way, hot chocolate becomes a comforting drink you can enjoy while also supporting your overall wellness. Number two, pomegranate juice. Pomegranate juice is something different to your gut microbiome because the the ruby red seeds of pomegranate which you know you get are used to make juice are contained something called a lager tenons. These are natural chemicals are so beautiful and they taste great. You can put them into a salad. There's lots of different ways you can you can do them, but when you juice them, one of the things that is wonderful is to be able to press the juice through the skin and because there's a lager tenons in the skin as well, so you get a lot more. You get like the knock out punch of these lager tenons when you juice with the skin. Now, what does that do? Those lager tenons in your body when you drink it. They, well first of all, they're also cancer starting. They're also antioxidant. They also lower inflammation, but one of the great things about they do is they stimulate your gut to secrete healthy mucus. And that's normal. It sounds a little gross, but actually our gut likes to stimulate, that leaves like some make mucus and the bacteria love to grow in the mucus. The bacteria growing in ucus in our gut is like flowers growing in a flower bed that's been properly fertilized. They sprout, they bloom, they really they they look great. And that's basically what a pomegranate juice actually doesn't our gut. It helps these bacteria grow really well. One of the bacteria grows really well is called acrimacia. Acrimacia, mu sinophila, mu sin like, like mucus. And that bacteria is a guardian of our health. It helps our immune system. It helps us fight cancer. It actually even appears to be able to help kind of make blood sugars good to be able to help control and prevent diabetes. And so that's a function that a simple juice that's delicious to drink and easy to make like pomegranate juice is so valuable. Pomegranate juice is not only refreshing and colorful, it is also rich in natural compounds that can support your health in several ways. One of the biggest reasons pomegranate juice is special is because it contains powerful antioxidants called eligitannins. Antioxidants help protect your body's cells from damage caused by harmful molecules known as free radicals. These molecules are created naturally in the body and also come from pollution, stress, and unhealthy lifestyles. Over time, too many free radicals can speed up aging and increase the risk of certain diseases. You can think of eligitannins as tiny protective shields that help defend your cells and keep them functioning properly. Pomegranate juice may also support gut health. Inside your digestive system, live trillions of beneficial bacteria that help with digestion, immunity, and even mood. Eligitannins are converted by these good bacteria into helpful compounds that encourage a healthier gut environment. A balanced gut microbiome strengthens the immune system and supports overall wellness. Researchers have also studied how compounds in pomegranates affect abnormal cell growth. Some laboratory studies suggest these plant compounds may help slow the growth of certain cancer cells by interfering with the formation of new blood vessels that tumors need to grow. While this does not mean pomegranate juice cures cancer, it shows how plant-based foods can support the body's natural defense systems. How drinking pomegranate juice can support your health. To get the most benefits, choose 100% pure pomegranate juice with no added sugar. The fruit is naturally sweet, and extra sugar can reduce some of the health advantages and add unnecessary calories. A good serving size is about 1 glass, around 8 ounces, or 240 milliliters per day. This amount provides plenty of beneficial nutrients without overdoing sugar intake. You can drink it in different enjoyable ways. Enjoy a plane for a natural energy boost. Mix it with sparkling water for a refreshing, low-gilt drink. Add it to smoothies or other fruit juices for a nutritious breakfast or snack. Number 3. Green tea and black tea. Tea comes from a plant and we know that plant-based foods are good for our health. That's now almost universally recognized. And the leaf of the tea, which is what we steeped from a sort of researcher's perspective, there are thousands of natural chemicals. We call them bio-actives because they interact with our biology and some of the compounds that are natural chemicals are like catechins, gallag acid, athianin, and thiaflavins. And they all wind up in a cup of tea when you brew it. And some of the amazing things that have been shown by research is that drinking tea actually can help prevent our cells from aging. So it's even has a, I'm sure the emperor didn't have the science, but appreciated that anti-aging properties of tea prevents our telomeres from shortening. So we stay our cells stay younger, slow down cellular aging. There's a polyphenol, everybody talks about polyphenols. I like to be specific. So the polyphenol tea that has been best studied in tea is called EGCG. Epegallo, catechin, galleid, EGCG, and green tea has a lot of it because it's closest to what comes off the tea plant. And then everything from that, old teas come from that downstream in terms of how they're prepared. But green tea has, you know, as much as 16 times that EGCG then some of the more processed are handled. Tea is one of the most popular drinks in the world, but it's more than just comforting. Both green tea and black tea contain natural plant compounds that can support your overall health. Green tea is especially known for a powerful compound called EGCG, epigallicatechin, galleid. This natural substance acts as a strong antioxidant. Antioxidants help protect your body cells from damage caused by harmful molecules called free radicals, which are linked to aging and many chronic diseases. EGCG also helps reduce inflammation in the body. Since long-term inflammation can contribute to heart disease, metabolic problems, and other health issues, drinking green tea regularly may help support the body's natural balance and repair processes. Black tea, although processed differently through fermentation, is also very beneficial. During fermentation, the tea leaves develop their own special group of compounds called polyphenols. These plant nutrients help support circulation, hard health, and cellular function. Some research suggests that the polyphenols in tea may also support the body's natural renewal systems, including stem cells, which help repair and replace damaged cells. While tea is not a medical treatment, it can support the body's natural maintenance and healing processes. Green tea and black tea can be very healthy drinks, but how you prepare them can make a difference in how much benefit your body receives. Health experts often suggest drinking about two to three cups of green or black tea per day. This amount provides a good supply of natural antioxidants without overdoing caffeine. You can enjoy tea, hot or cold, depending on your preference, both offer similar health benefits. To make your tea even healthier, you can add simple natural ingredients. A squeeze of lemon helps your body absorb antioxidants more effectively. Vitamin C and lemon protects these beneficial compounds and allows your body to use them better. A small amount of fresh ginger adds flavor and provides extra anti-inflammatory properties, which may help support digestion and overall wellness. It's best to avoid adding sugar because excess sugar adds unnecessary calories and reduces the healthy impact of the drink. Many people also add milk, but some studies suggest milk proteins may slightly reduce how well certain tea antioxidants are absorbed by the body. In simple terms, a healthier tea routine looks like this. Drink two to three cups daily. Enjoy it hot or iced. Add lemon or ginger for extra benefits. Skip sugar and limit milk. Prepared this way, tea becomes more than just a relaxing beverage. It turns into a simple, daily habit that supports hard health, reduces inflammation, and helps protect your cells over time. | ↗ |
| 38 | NIE SINGAPORE | Induced Pluripotent Stem Cell iPSC | 89919 | 1823 | 50 | 65.4 | positive | 5:04 | We often hear in Chinese myths that there was an elixir of eternal life that would grant the people who drank it immortality. Of course it was brushed aside as a myth, but what if I said that this could actually be a reality in the years to come? In 2006, Shinya Yamanaka, a Japanese Nobel Prize-winning stem cell researcher, introduced induced pluripotent stem cell technology. This technology was revolutionary as it allowed scientists to convert any mitotic cell into a stem cell. The mitotic cells are artificially induced to revert back to a state where it can specialise into different cell types. It is like taking a cake and reverting it back to flour and eggs and changing it into another food, like cookies. Not only that this defied convention, as it was thought cell differentiation was not reversible. It also opened up countless possibilities in potential medical treatments. Before we go more in depth about IPSE, we need to first learn about PSC. Pluripotent stem cells are cells that are able to differentiate into most cell types. In other words, these stem cells which are not specialised when placed in a certain environment will specialise into different cell types. As we develop as an embryo, these cells are what form our organs, limbs, bones and so on. In the past, these cells were harvested from embryos in the blastocyst stage. However, this was unethical as this resulted in a death of the embryo and was not well received by the public as a possible regular treatment. IPSEs were made by taking a mitotic cell from the patient's body, usually skin cells, and treated the cells with specific transcription factors. Opt for, Clif4, Sox2 and C-Mike proteins. These transcription factors that were added outcompeted the other transcription factors and took control of how the cells behaved by changing the packing of DNA and the level of expression of different genes. This caused the mitotic cell to revert back to its pluripotent state. IPSE has many benefits for patients. For example, patients with severe burns can have their skin grown in the laboratory and later grafted onto them. One limitation of current skin grafting methods is that when transplanting the skin from one area of the body to the burn section, structures such as hair follicles and blood vessels are lost. By growing the skin from stem cells, the skin graft would have both hair follicles and blood vessels, thus improving their survival rate. Another group of people would be patients suffering from organ failure. Looking back at our video on Xenograph, we learnt that shortage of organs to treat organ failure has led to doctors looking for alternative sources and the current solution is humanized pick organs. However, with IPSE, patients would be able to grow another organ with their own cells and DNA, thus reducing their dependency on organ supply and they need not worry about organ rejection or incompatibility. Lastly, IPSE can be transplanted into the pancreas of diabetic patients and they can differentiate into pancreatic cells to produce insulin, thus reducing the need and reliance on long-term medication. With IPSE being such a complex process, it is without doubt that it would not be 100% efficient. Experiments have shown that this process of reverting a mitotic cell into a pluripotent stem cell may not always be successful and harmful mutations could occur instead, leading to higher risk of genetic diseases such as cancer. Also, IPSE is an expensive process and the cost of the patient has to bear may be greater than the benefits it can bring. An ethical concern is that it would be possible to create an egg and a sperm from normal skin cells to create a human being. Some people may see this as a problem as we are able to create human embryos and life. Also with the advancement of technology, it could be possible to edit the genes in the sperm or egg to produce human beings with desirable traits. Even though IPSE comes with high risk, we cannot deny the progress it will bring to medical therapeutic advancements. As such, perhaps to mitigate these risks and concerns, we can have strict regulatory controls in place. What do you think are some suitable controls to prevent the abuse of this elixir of eternal life? | ↗ |
| 39 | Animated biology With arpan | iPSCs: Turning Any Cell into stem Cells. But how? #animated_biology # ... | 9799 | 268 | 4 | 65.2 | positive | 1:52 | IPSCs are induced pluripotent stem cell grown in the lab and these IPSCs are derived from any somatic cell like a skin cell. There are four magic factors known as Yamanaka factor which can convert any cell into IPSCs and this is the Nobel-winning discovery by Shinya Yamanaka. In this experiment Shinya Yamanaka misexpressed four transcription factor, O3, Cemic, Sox2 and KLE4 in a mouse fibroblast cell and that got converted into a cell type which is very similar to a stem cell. It can now give rise to cells of mesodermal lineage endoderm or ectodermal lineage. These are IPSCs but how does Yamanaka factor work? Any somatic cell has its specific gene expression program. When these transcription factors are misexpressed, these gene expression program has to be shut down and eventually stem cell like gene expression network or modules would be upregulated and act in the cells to make them stem cell like. IPSCs has multiple applications. In 2017 first time IPSCs was used for the treatment of macular degeneration. This was led by the work of Dr. Masau Takahashi. She took cells from AMD patients converted them into induced pluripotent stem cells in the lab. From the stem cells specific differentiation protocol converted these cells into retinal pigmented epithelium and that was injected into the retina of AMD patients which lead to a partial cure. Now IPSC has huge potential in terms of clinical application. So what are the clinical application of IPSCs? Want to know more? You have to watch the full video! | ↗ |
| 40 | Doctor Leana⚕️ | "THIS Forgotten Herb TRIPLES Stem Cells & REVERSES Aging" – Take This ... | 29627 | 2948 | 82 | 65.1 | positive | 27:25 | No transcript | ↗ |
| 41 | Medtronic | How will regenerative medicine transform healthcare? | 7189 | 305 | | 65.1 | | 0:27 | Just understanding regenerative medicine, how it could work, something that's out there, we look at it for diabetes. It's not right around the corner. It's decades off, probably still, but where you can regenerate a pancreas. We have to stay on top of these things because in healthcare, you can't have the innovators to Lama. You've got to embrace new technology because the stakes are so high. | ↗ |
| 42 | Dr. Lindsey M. VanDyke, DO, FACOI, FEAA | Can You Imagine? A Possible Cure for Type 1 Diabetes with Stem Cell Th... | 3968 | 114 | 7 | 65.1 | positive | 1:07 | Dr. Van Dyke here, board certified endocrinology and I just wanted to make sure you know about some breaking news in the endow world. A recent study was just published about a new innovative therapy that can possibly cure type one diabetes. It was a small study but these patients who receive stem cell therapy have now been functional without insulin for several months and this is incredible. For anybody who has lived with type one which remember is an autoimmune condition that destroys your ability to make your own insulin. They have to live with injections multiple times a day of insulin. Insulin is one of those hormones that if you can't make it and you don't take it, you'll die. So this is a big deal that if this really comes through for us, then we're talking about insulin pumps and multiple daily injections of insulin, be in a thing of the past. Very exciting and we'll keep you apprised of any updates that I hear. | ↗ |
| 43 | Peter H. Diamandis | Harvard Prof Reveals Age-Reversing Science to Look & Feel Younger w/ D... | 290999 | 8580 | 1416 | 65.0 | positive | 2:23:38 | No transcript | ↗ |
| 44 | Doctor Becker | 600mg of This Kills Cortisol & Doubles Your Stem Cells While You Sleep | 26775 | 1424 | 78 | 64.6 | positive | 40:12 | No transcript | ↗ |
| 45 | The Health Lens | Dark Chocolate Can Double Your Stem Cells! #drwilliamli #viral #cancer | 210 | 11 | | 63.9 | | 2:04 | of cacao, but I will tell you that cacao has been shown to actually double the number of stem cells flowing in your bloodstream just by having two cups of hot chocolate made with 80% high flavanol chocolate dark chocolate. Come on. Yeah, that's been done in people 60 year olds with heart disease. So wait, what happens when you when you drink or you you eat this dark chocolate. Okay, it happens. Yeah, the polyphenols in this dark chocolate that we we know what they are they're called pro-antho-sianidins. So I'm a scientist. So my job is to actually know what are what the inside chemicals actually are. These are natural chemicals. All right, most people don't need to know that, but you drink it and taste good. That's all you need to know, but but I'll tell you these these natural chemicals found in cacao actually trigger a reaction in your body so that they call out the stem cells. So it is literally like bees flying out of a hive. Can double the number of stem cells and what's the what's the practical impact? Well, there was a study done at UCSF in San Francisco that looked at 60 year old men with heart disease. So these are people whose blood vessels were already not doing so well and their blood flow wasn't going so well either and their blood vessels were kind of sick. That's kind of the definition of heart disease. By having the stem cells coming out, they were able to actually double the resiliency, the function of their blood vessels. So they got better rebound, the better agility, their blood vessels are in better shape. Dr. Lee highlights that high flavonal cocoa drinks such as hot chocolate have been shown to double circulating stem cells which help to repair tissues and blood vessels. Cacao is rich in prosianidins and flavinols that inhibit abnormal blood vessel growth in gyogenesis, benefiting conditions like cancer, cardiovascular disease and diabetic complications. | ↗ |
| 46 | TEDx Talks | Stem Cells: The Future of Regenerative Medicine | Valentina Vasquez | ... | 28815 | 556 | 31 | 63.7 | positive | 7:57 | Transcriber: Jay Kallem
Reviewer: Sarah Abdelrahman [Stem Cells: The Future of Regenerative
Medicine: Valentina Vasquez] When I say the words terminal illness,
what do you think of? Oh, unfortunately, the word that
comes to my mind is death. In 2019, 121,500 deaths were recorded
due to Alzheimer's disease. But what if this disease
could be reversed? And what if stem cells were the answer? While diseases like Alzheimer's
are devastating, I can't help but wonder how these
neurodegenerative diseases manifest in one's brain and why scientists
have yet to find a cure for them. I remember when I was younger, I had
a conversation with my parents, and they told me that when my
brother and I were born, stem cells were taken from my mother's
umbilical cord and stored in a cell bank. Naturally, I was confused, so I asked why? They said that stem cells were being
used for neurodegenerative diseases such as Alzheimer's, Parkinson's,
and Huntington's disease, just to name a few, and that these cells
would be useful for me later in life. I was so amazed at this concept, that a part of me could
be used to heal myself from possible diseases I may
acquire in the future. These minuscule cells furthered my
love for science and medicine, and I became more interested in learning
about the foundation of life itself. Cells or in this case, stem cells. Stem cells have the unique ability to
develop into practically any cell within the body. But before I explain
the nitty gritty, let me first tell you how stem cells
really came to my attention. So after that conversation with my
parents, I didn't put too much thought into stem cells,
or the fact that I had some stored in a cell bank for quite some time. But my amazement with these cells
started up again when I gained a new found interest in dementia and the
influence it had on people's lives and the effect it had on their brains. I started to research Alzheimer's,
which is a form of dementia, as dementia is just the umbrella term for several diseases affecting
cognitive function. And I came across the term stem
cells more frequently. But at that time I didn't know much about the topic other than what
my parents told me about the advances being made in medicine
using stem cell application. Now, if you want to have a basic
understanding of stem cells, you have to understand basic human
development as it begins with pregnancy, which happens after a sperm cell
fuses with a woman's egg, which then develops into a zygote
and then a blastocyst. And this is where the magic happens. A blastocyst is a cluster of
dividing cells made by a fertilized egg roughly five
days after fertilization. This is where the enormous surplus of
embryonic stem cells are located, and it is at this stage, in particular, where these pluripotent
stem cells show the most promise. And I know, I know,
most of you are probably thinking, Valentina, you can't
be throwing words like embryonic stem cells and pluripotent around with no
explanation. But don't worry, I got you. So any person that begins to research stem
cells will naturally become overwhelmed by the many components and
groups that seem to overlap somehow. Because I know I was. So let's start
with the word pluripotent. Pluripotent was a term I often encountered and I was under the impression that it
was this big group of stem cells with smaller groups, and within one of those
groups being embryonic stem cells. But this is not the case. The word
pluripotent actually means many potentials. So in other words, these cells have the potential to develop
into any cell within the body. So embryonic stem cells are pluripotent. You can think of these cells as
like the roots of a tree. Just as tree roots give rise to different
branches and leaves, pluripotent stem cells have the ability to differentiate
into various cell types within the body, forming the branches and trees of
the body's tissues and organs. Now, adult stem cells are another
type of stem cell group typically found in developed
tissue throughout the body. You can find them in
the brain, skin, heart, liver, and bone marrow, and these cells
typically have the job of repairing dead or damaged tissue throughout our body. And these are the cells that
heal cuts on our skin, for example. They're also referred to as somatic stem
cells because they're non-reproductive and they also typically scarce. This
makes them challenging to study. There are also multipotent, which means they do have the ability to
develop into more than one cell type, but means they are. They just have a more limited ability than
pluripotent stem cells. Now, iPSCs or induced pluripotent stem
cells are another type of stem cell group made by reprogramming adult stem cells. This process includes introducing a set
of factors such as dermal fibroblasts, which are cells that help heal
the skin from injury. These cells are then genetically
reprogrammed to an embryonic stem cell like state
or a state of pluripotency. iPSCs show much promise in being used in
personalized medicine due to their ability to develop into more than one
cell type when programmed to do so. Now, the last type of stem cell group I want to share with you all today are
MSCs or mesenchymal stem cells. MSCs are adult stem cells commonly found
in the bone marrow and umbilical cord. And these are actually the cells that my
brother and I have stored in a cell bank. Despite being found in the umbilical cord, MSCs are classified as adult stem
cells, solely based on property and function rather than tissue origin,
also meaning that they are multipotent. Stem cells are being used in ways people
50 years ago would have believed to be science fiction, but they still
have a long way to go. The field that stem cells are being used
in today is called regenerative medicine, and it’s centered around implementing
and creating new treatments to aid the body and naturally
healing and repairing tissue and replacing lost functionality brought
on by aging, illness, injury, or defect. Adult stem cells show much potential
from being able to be used to treat type one diabetes, which they would
provide insulin producing stem cells and cardiac cells to replace damaged
cardiac muscle after a heart attack to neurological diseases
in which they would regenerate lost neurons in the brain or spinal cord. In a study done by Stanford’s
Dr. Marcus Wernig, stem cells were found to reduce brain abnormalities
typical of Alzheimer’s in mice. This is actually a really good indicator
that it will be promising in humans, as mice have a similar anatomy. Stem cells have also begun to be tested
in sports medicine regarding the treatment of damaged tendons,
torn ligaments, and other muscle and bone injuries. To put it into perspective, imagine you
are a great athlete who tears their ACL. Typical surgery would mean
a long recovery process and uncertainty about your future career. But with stem cell therapy, the damaged
area would be injected with stem cells, leading to a shorter and less
invasive recovery process. So what does this mean for our future and
the future of regenerative medicine? And mesenchymal stem cells are also
being used as an extensive tool for diseases such as stroke
and Alzheimer's. But the reason that there’s
no cure for these diseases yet, is that stem cell therapy will
only replace damaged cells, but not cure the genetic root cause that
most of these neurodegenerative diseases typically arise from. So what does
this mean for our future and the future of regenerative medicine?
Well, firstly, let’s celebrate an already successful treatment
used in medicine today, which is a blood stem cell
transplantation typically used for cancer patients to replace dead
and damaged cells within the body. And back in In 2018, Japanese
scientists conducted a clinical study where they used
neurological material derived from iPSCs to treat Parkinson's disease. And while the results were very promising, this treatment is years from clinical use. I believe that the future of stem cell
therapies will transform disease outcomes for many patients and lead to many more
groundbreaking scientific discoveries, and it’s why scientists and
doctors should continue to advocate for the importance of stem cell research. Because as this amazing area of
medicine continues to expand, I urge you to support stem cell research
by donating to stem cell initiatives that work hard to advance
this area of medicine and share their findings while doing so. And as you walk out of here today, I want you to think about how stem cell
research is reshaping modern medicine as we know it and is changing lives and
could one day change yours too. Thank you. (Clapping) | ↗ |
| 47 | Integrated Aesthetics | Stem Cell Therapy for Hair and Skin: Meet Acorn | 1901 | 29 | 8 | 63.7 | positive | 6:23 | Could this little bottle be the future of anti-aging? Let's talk about it. Aging is as old as time, but anti-aging treatments, not so much. From Cleopatra's legendary Donkey Milk Baths in 69 BC, two travelers chasing the fountain of youth in the 1500s, and then again in 2002, when the FDA regulated and approved Botox for frownlines, we've always looked for ways to slow the clock. Fast forward today, in modern sciences, taking anti-aging treatments to a level that Cleopatra never would have dreamed of. One of the biggest game-changers was PRP, or platelet-rich plasma, popularized by the Kardashians in the famous vampire facial. Micro-needling with PRP is incredibly helpful to address fine lines and wrinkles and improving skin tone and texture using your own blood's healing abilities. Then came exosomes, their tiny little particles in our own stem cells. These are packed with a per 400 growth factors compared to PRP's 25. This can help with one's ability to reduce inflammation, boost our own collagen, and provide younger, smoother looking skin, and even hair restoration. But here's the catch. Most exosomes come from donors, meaning you're using someone else's cells. And while using donor cells is very effective, some patients may feel uneasy about using another person's biology on themselves. So the big question is, what if you could use your own cell instead? And that's where Acorn comes in. Acorn Biolabs is a Canadian company, and they have developed this incredible technology where they take your own tissue, your own cells, and create a personalized regenerative medicine that is tailored for you by you. It's using a tolligous tissue, meaning it's your own. They harvest stem cells from there, they can bank it, and they can then culture it and derive products from it that we can now use for regenerative purposes. One of the great advantages of using your own stem cells and extracting the key elements of that is that your stem cells and the components derived from there are much more potent than your own PRP, which is platelet-rich plasma. So we already used platelet-rich plasma all throughout aesthetic medicine, whether it's for facial rejuvenation, hair restoration, for sexual wellness. Now we have the ability to use your own stem cell derived products, which are more potent, somewhere even up to 34 times more potent than PRP. And we can use it for very similar applications everywhere where we currently use PRP. What's really innovative about Acorn's technology is that if I'm doing a platelet-derived procedure, then I'm drawing blood today, and I'm using that product today, which means that the platelet's age is reflection of my current age today. With Acorn's technology, what you're doing is you're harvesting your stem cells today, and they can be used indefinitely as your age. You're freezing the youth of the stem cells for today for future applications. That in itself is a really big innovation, because as we age, our cells just kind of lose a little bit of their luster. They don't function as well. The amount of regenerative cells that we have in our body starts to decline with age as well. So being able to capture presently our current age and using that benefit as we get older is very potent and powerful. So how do they do it? The answer might be closer than you think. It's on your head. Well, your hair follicles to be exact. By taking the hairs, the benefit of hair itself is it's a really diverse cell mixture, and it includes stem cells or pluripotent stem cells, which can then differentiate into different cell types. In the lab, they've even shown that these stem cells can be turned into bone cells and to fat cells and to kidney cells or pancreatic cells and others. So the future of this technology is very exciting, although it may be in the distant future, but there's already applications that are used today, and that is with the derivation of secret homes, which is derived from your own stem cells. So how does it work? It starts with a quick and clinic visit where about 50 hairs are plucked from the scalp. From there, your stem cells are collected and preserved, and essentially we're putting your aging on ice. It's then used as a personalized regenerative skincare product. The treatment pairs well, post-laser, as well as micro-needling and other aesthetic services, improving skin healing and long-term rejuvenation. So what sets it apart? Secret homes are products from your own personalized stem cells. So that already makes it unique and different from anything else in the market right now. Today we can order exosomes that are derived from donor platelets or from donor, umbilical cords or other sources where exosomes are derived, and what exosomes are are the signals that our cells use to communicate with each other. So our cells release signals to communicate to a different cell, and that's how this communication in our body happens. Some of those communication cells are really good for things like wound healing, and those have some very strong regenerative properties. But if you can take your own personalized exosomes and really focus on the ones that are going for regenerative purposes by going after the stem cells, that's going to be huge. In addition, they can recruit other things that stem cells secrets separate from the exosomes like growth factors and extracellular matrices components that are really important for things like hair growth, tissue regeneration, collagen regeneration, elasticity, and more. So this patented process allows us to create individualized and unique treatments just for you. No guesswork and no donor material. It's just your cells helping you in your skin look and feel its best. So is this little bottle the future of anti-aging? It just might be. How no brown cow. My audio is incredible. I'm going to redo that. Oh my god. Down our. Okay. I will get this line. It's a hard one but it's a good one. Being regenerative, regenerative. | ↗ |
| 48 | TEDx Talks | Tissue Engineering for Regenerative Medicine | Warren Grayson | TEDxBa... | 54904 | 943 | 25 | 63.5 | positive | 11:22 | I'm a little bit more focused on my music. I'm a little bit more focused on my music. I'm a little bit more focused on my music. Close your eyes and visualize someone close to you. Maybe a mother, a close friend, maybe a favorite uncle. Open your eyes. For most people, given that exercise, they're going to see the face of the person or the close loved ones. Not their elbow. And so the reason is that the face is closely associated with our identities. The face is what we see when we look at other people. This is how they recognize us. It's associated with our sense of self. And so as we examine what are the definitive features of the face. Let's look at this iconic beauty, Grace Jones. Only the first things you might recognize might be the non-traditional haircut. It might be the piercing stare. But I would also suggest that the other things you see are the broad forehead. You can see the angular features, the high cheekbones, the square jaw, the pointed chin. These things are dictated by the structure of the underlying facial bone. Our facial bone determines our appearance. It determines our sense of self. And when that bone becomes damaged, it damages our sense of self. Here's a patient. Let's call her Jane. Jane had a bone cancer on the left side of her face. That had to be surgical removed and it dramatically altered her appearance. Jane's left eye is drooping. Her nose is indented. And though it may not be very easy to see right here, her face is also sunk in on the left side. This is what the medical imaging shows us about Jane. On the right side, the bone is completely intact. On the left side, that orbital bone that kept her eye in place has been removed. And then her eye is drooping. The entire mid-facial bone had to be removed. Pancy changes to appearance of a nose and a face. A patient like Jane is going to require a bone graft to reconstruct her face. But she's not unique. Every year within the United States, there are up to 200,000 people who require bone grafts for skull and facial reconstruction. At a health care cost of up to $1 billion. So let's imagine someone like Jane who's living in the United States, one of the most technologically advanced countries in the world, with access to the best health care, with access to the most talented surgeons, how would she be treated? This is how they treat them currently. This is the state of the art treatment. It's called autografting. Where I'm going to take a bone from another part of your body, often it's a leg bone. And I'm going to transplant it into the facial region. This is what Jane looks like during surgery or surgical planning. That leg bone has been broken up into four different pieces and reconstructed like a puzzle trying to put it back to reconstruct that facial appearance. This is going to result in a marginal improvement in Jane's appearance. And I've come to believe that this approach is primitive. I, together with my colleagues, are working on approaching regenerate bone that has the appropriate anatomical structure. That is a living tissue so that the patient grows and changes that bone grow and change along with the patient. But also that bone to become a prize of the patient's own genetic material so that it doesn't have any rejection, doesn't suffer from any rejection. We call this approach tissue engineering. Tissue engineering, we start with a scaffold. And that scaffold is very important. So, its scaffold is going to determine the exact shape of tissue that is going to regenerate. And so we make that scaffold in the exact shape of the bone that we would like to regenerate in this patient. Discaffold is also porous. And what that does is allow cells and blood vessels to grow inside of it. So we can form living tissue, healthy tissue. But the scaffold has another really critical feature. Once that new bone forms, that scaffold should degrade away, leaving only biological tissue. So that scaffold, we are going to add stem cells. The stem cells we get from the patient's own fat tissue. So for those of us who bear begots, love handles, this is our evolutionary advantage. We can take those stem cells and isolate them from that fat tissue. And we keep it in a solution. And that solution we're just going to take and drip onto that scaffold so that it spreads uniformly throughout. So that when the cells go, they can form bone throughout that entire scaffold tissue. But the cells have an important characteristic. The stem cells can form different types of cells within the body. And so it's important that when you put those cells inside of that scaffold, they appropriate signals so that they know they should form bone and nothing else inside of it. And so we add to those stem cells and scaffold, we add bone signals. We had done this with any labs several years ago. We tried to combine all three of these features. These stems, these stem cells, these scaffolds, and the bone signals. And what we showed was that after a period of five weeks, we were able to grow a piece of jaw bone. This is the piece that is right at the top of the jaw. This part is in front of the air. It what's allowed us to open and close our mouth to speaking and to chew. And so we thought if we could regenerate piece of jaw bone in the lab outside of the body, the next logical step is to see what we can do inside the body. To do this, we work with mice. Now mice are interesting in that they regenerate really well. And so for us to test this within mice, what we did was to create two holes in the skull of the mice. Taking very good care, not the damage, the underlying bone, the brain tissue. Within those holes, what we did was to put scaffolds and stem cells and bone signals. This is a CT image of the mouse that shows only the bone. It's like a cat scan for mice. On the left side, you can see the hole that we created, one of the circular defects that we created that has is scaffold only inside of it. On the right side, we've put the scaffold and we've populated that scaffold with stem cells. And it could start to see the beginnings of some bone forming inside of the air, shown by the little nodules that you see on the inside of the circle. However, once we add those bone signals to that defect, we see a dramatic difference. We can regenerate large quantities of bone within that defect after a period of six weeks. That new bone that is forming is taking the shape of that scaffold that we've implanted inside of that defect. And so for us, what we feel is that we have the fundamentals of a way to revolutionize the way that patients like Jane would be treated once she comes to the clinic. So how would that change the way Jane is treated currently? Currently, we will take a CT image as we've done before of this patient. So the surgeon will take a CT image when the patient comes in. What if the patient is missing bone? Well, we can digitally include that bone inside of it. And so at the end of this, whether it's a cancer patient or someone with a congenital defect would never have had bone in that place, we can still render what that three-dimensional bone volume would look like. With that three-dimensional bone volume, we can take it and we can 3D print scaffolds in the exact shape of the bone that we are trying to regenerate. Or what is unique about this 3D printing? Can anyone with a 3D printer at home do the same thing? This 3D printed material is made out of a bio-degreeable polymer. So that over a period of time is going to disappear within the body. But not only that, we also created new materials so that within it, the bone signals can actually be included while we are doing this 3D printing. So this is what we're going to take. And this is what we're actually going to take back to the surgeon, give to the surgeon so that while this patient is on the operating table, the surgeon can extract her stem cells, he can open up this scaffold sterile. As you would do with any bandage or any plaster, but the difference is here that in this case, we have a customized bone for that patient. You put the stem cells into the scaffold and then immediately transplant that scaffold back into the surgical, into the bone defect. And this is how we're going to start within a few weeks to regenerate bone inside of that patient. This is going to revolutionize the way that patients like Jane, cancer patients, trauma victims, soleas coming back from birth, from walls or accident victims, or even children born with missing bones. We're going to revolutionize the way that these people are treated in the healthcare system. We're going to change the face of medicine. My colleagues and I feel blessed that we can work on such challenging, but also a very rewarding topic. We, and so each day as we go to work, as we work on these, and innovating new paradigms, we never forget the fundamental aspect of our system. We never forget why we do the research. Thank you. Applause | ↗ |
| 49 | Doctor Leana⚕️ | "Chew This Tonight" – Most Powerful Way To REBUILD Stem Cells & Repair... | 53347 | 3259 | 94 | 63.4 | positive | 39:07 | No transcript | ↗ |
| 50 | Ioana the Iguana | Induced Pluripotent Stem Cells // Engineering Explainers #2 | 5521 | 141 | 5 | 63.4 | positive | 4:19 | Induced pluripotent stem cells. You may have heard these words thrown around in articles about regenerating organs or making human tissue, but what actually are they and how do they work? Let's start from the beginning. Cells are the building blocks of all living tissues. They come in a variety of shapes, sizes, and functions. Cells are a generalized type of cell from which specialized cells develop. They can either make copies of themselves or they can differentiate into any tissue, like the brain or the liver or the heart or anything else. If we go even deeper we can talk about embryonics themselves, which are basically the earliest cells in an embryo before they start to differentiate into specific tissues and organs. We call them pluripotent to mean that they have the ability to become any cell type in the body. So far so good, but what does it mean to induce pluripotent stem cells? As you can imagine, harvesting embryonic stem cells is not that easy and it comes with a range of ethical issues. So in 2006 researchers came up with the idea to make their own stem cells in a lab without the need for embryos. Sure enough their idea became reality. In 2012 Sir John Gordon and Shinia Yamanaka jointly received the Nobel Prize in Physiology and Medicine. They discovered that mature cells can be reprogrammed to act like pluripotent embryonics stem cells. The procedure is surprisingly simple. A hair follicle or a very small piece of skin is collected from a patient. Then it's placed on a dish and four proteins called transcription factors are added. They are nicknamed the Yamanaka factors and they are oct 3, 4, KLF4, C-MIG and SOX2. After a few weeks the cells are reprogrammed to look and behave just like pluripotent stem cells. So now we have a petri dish full of pluripotent stem cells. What can we do with them? We take a page out of the developmental biology book and effectively guide the stem cells to become whatever we want them to become. We place them in a soup or culture medium that simulates our desired final tissue and we add the growth factors that are expressed during development. So if we want to make a motor neuron we add the chemicals that normally transform an embryonic stem cell into a neuron and same for any other cell type. We follow the body's recipe to make any tissue we desire. Now I know this sounds a bit like magic and it totally blew my mind when I first encountered it. But there are in fact some obstacles and rules to follow. It takes months to go through the entire process and the reprogramming efficiency is not great. But it is an extraordinary feat of science. To be able to just collect a piece of skin or a strand of hair, make it behave like a pluripotent stem cell and then just instruct it to become a completely different type of cell. So what's next? At the start of this video I mentioned that you have probably heard of IPSEs in the context of making artificial organs and that is definitely an area of research but there is so much more to stem cells than just that. Researchers can model disease using IPSEs from a patient to analyze the phenotype and understand the physiology of the disease. Also they can bypass clinical trials and instead just test drugs directly on the differentiated cells. Finally, IPSEs can be used in cell or gene therapies. IPSE-based treatments have been researched for a large number of diseases such as Parkinson's disease, ALS, diabetes or various blood and heart diseases. I hope you enjoyed this video and learned something new today about induced pluripotent stem cells. Thank you for watching. Don't forget to like, comment and subscribe for more science content. | ↗ |
| 51 | The Proof with Simon Hill | Biology of aging: Cell Reprogramming | Dr Matt Kaeberlein | The Proof ... | 1531 | 47 | 1 | 63.3 | positive | 0:55 | If you take reprogramming to its sort of ultimate, you can actually take differentiated cells, so fibroblasts, for example, that skin cell, and reprogram them all the way back to a pleripotent state. So they completely lose their fibroblast identity. So it turns out that a lot of the developmental processes that allow for differentiation of cells and ultimately tissues and organs are largely mediated by epigenetic changes. Those very specific epigenetic changes then lead to certain genes getting turned on, which give the cell its identity, if it's going to be a heart cell, a myosite, or a skin cell. So yes, we're talking about gene expression, but these defined epigenetic changes that go along with differentiation, the first thing they do is turn on genes that then give that cell its identity. And you can reprogram cells all the way back to this undifferentiated or D differentiated state. | ↗ |
| 52 | khanacademymedicine | Stem cells | Cells | MCAT | Khan Academy | 452594 | 5953 | 99 | 63.2 | positive | 11:54 | So, let me give you an analogy here. When you're still an adorable little baby, you were just bursting with potential. You could decide to be a pilot, or a doctor, or a journalist. You had the potential to specialize into all sorts of different careers. And as you got a bit older, you got more and more committed down a certain pathway. And the decisions that you made moved you further and further along this pathway, right? Well, it turns out that stem cells operate in a similar way, going from unspecialized to more specialized as they get older. So, let me show you what I mean by that over the course of this video. And let's actually start back at this zygote here, the cell that results when sperm and egg fuse, because that's really where our stem cell story kind of begins. So, the zygote starts to divide, right, by mitosis, until it reaches the blastocyst stage. This hollow ball of cells here is called a blastocyst. And here, things start to get a little bit more interesting. So, in a blastocyst, there's this little grouping of cells down in here referred to as the inner cell mass. And this is a really special little bunch of cells that go on to become the embryo. So, these are called stem cells. And what they can do as stem cells is they can specialize into several other cell types. So, we actually call them pluripotent stem cells. Plurip, meaning several, and potent referring to these stem cells' ability to actually do this differentiation. So, during development, these inner cell mass pluripotent stem cells can differentiate into any of the more than 200 different cell types in the adult human body, when given the proper stimulation. So, it's kind of incredible to think that every single cell in your body can trace its ancestry back to this little group of stem cells here. And actually, if you ever hear anyone talking about embryonic stem cells, these are the ones they're referring to, these ICM stem cells. So, is this the only place we can find stem cells here in the developmental structures? We used to think so, but it turns out that in mammals, there are two main types of stem cells. Embryonic stem cells that we just saw, and somatic stem cells, which are found in every person. So, the embryonic stem cells are used to build our bodies, to go from one cell to trillions of specialized cells. And the somatic stem cells are used as sort of a repair system for the body, replenishing tissues that need to be replaced. And they can't repair everything, but there's a lot of everyday repairs that can happen because of our stem cells. So, in skin, for example, this outside layer is the part of our skin that we can see and that we can touch, right? And it's made of these waterproof, pretty rugged epithelial or skin cells. And interestingly, although they are pretty rugged, you're constantly shedding these skin cells. They actually just sort of fall off or get rubbed off during everyday activities like when you're putting your clothes on. And then the ones from underneath them just sort of move up and take their place. So, you shed them and you lose almost 40,000 of them per hour. So, if we want to have any hope of keeping our skin, we kind of need a way to replace these cells. And that's where stem cells that live in our skin come in. Actually, our skin cells are shed and replaced so often that it only takes a month for us to have a completely new skin, like literally one month, entirely new skin. It's outrageous. Anyway, deep within our skin, there's this layer of stem cells called epidermal stem cells. And their job is to be continually dividing. So, you can see them dividing here, dividing, dividing, dividing, and making new skin cells that go onto my great upward as the multiple layers of our skin. And their goal is to eventually replace these ones up here on the outside that get damaged or worn out and fall off. So, it's this kind of activity here which show off our stem cells role as our regenerative cells. Now, let me just highlight a few differences between our mature skin cells over here and our stem cells down here. They are very different. Mature cells are not the same as stem cells, and this principle goes for really any mature cell versus any stem cell. So, the mature cell is already specialized. It already has a really specific function. For example, our outer layer of epithelial cells here, they have a protective function against the outside environment. And you know, just thinking of other adult cell types, right? Like, muscle cells have a contractile function. And neurons have a message sending function. And bones have a rigid structural function. So, all these adult cells are already nice and specialized. They've grown up and decided what they want to do for living. Whereas stem cells are not like that at all. Stem cells are unspecialized. But they still have a really important job, which is to give rise to our more specialized cell types like these cells here. Okay? And actually, in order to be considered a stem cell, and this goes for the embryonic stem cells we met previously and the somatic stem cells we're meeting now, to be a stem cell, you'd need to possess two main properties. The ability to self-renew, meaning you can divide and divide and divide, but at least one of your resulting cells remains a stem cell. It remains undifferentiated. And you'd need to have a high capacity to differentiate into more specialized cells when the time comes. So, remember, this is also referred to as having some degree of potency. And there's actually a few different types of stem cells, and some of them can turn into more types of cells than others, some are more potent than others. So, this epithelial stem cell we saw here is actually one of the less potent types of stem cell. In other words, these stem cells can only divide and specialize into more epithelial cells. So, there are source of epithelial cells, sure, but only epithelial cells and not any other cell type. So, we call them unipotent, referring to their ability to only create one type of cell. But let me show you another example here of a multi-potent stem cell. Let's look at this guy's femur, his thigh bone, which is where our blood cells are made inside bone marrow and our bones. So, you might know that our red blood cells have a lifespan of about four months. So, that means that we need to be constantly replacing our red blood cells or we'll run out, right? Well, in our bone marrow, we have what are called hematopoetic stem cells, which are our blood-making stem cells. And these are pretty special. They're multi-potent stem cells, which means they can give rise to many types of cells, but only ones within a specific family. In this case, blood cells and not, for example, cells of the nervous system are the skeletal system. So, our hematopoetic stem cells are always busy churning out new blood cells. Red blood cells to carry oxygen for us and white blood cells to keep our immune system nice and strong. And for a more clinical example, with blood diseases like leukemia, certain blood cells will grow uncontrollably within a patient's bone marrow, and it actually crowds out their healthy stem cells here from being able to produce enough blood cells. So, as part of treatment, once the leukemia cells are cleared from the bone marrow with usually chemotherapy or radiation, doctors can actually put more hematopoetic stem cells back into the bone marrow that then go on to produce normal amounts of blood for the person again. So, this is probably the most common use of stem cells in medicine as of now. And you can actually find these multi-potent stem cells in most tissues and organs. So, for example, we have multi-potent neural stem cells that slowly give rise to neurons in their supporting cells when necessary. And we have multi-potent messing chymal stem cells in a few different places in the body that give rise to bone cells and cartilage cells and adipose cells. So, you might be wondering after seeing our epithelial and our hematopoetic stem cells dividing, why aren't these cells being used up as they divide? And that's a really good question. So, stem cells have two mechanisms in place to make sure that their numbers are maintained. So, their first trick is that when they divide, they undergo what's called obligate asymmetric replication, where the stem cell divides into one so-called mother cell identical to the original stem cell and one daughter cell that's differentiated. So, then the daughter cell can go on to become more specialized while the mother cell replaces the stem cell that divided initially. The other mechanism is called stochastic differentiation. So, if one stem cell happens to differentiate into two daughter cells, instead of a mother and a daughter, another stem cell will notice this and makes up for the loss of the original stem cell by undergoing mitosis and producing two stem cells identical to the original. So, these two mechanisms make sure their numbers remain nice and strong. So, we've looked at embryonic stem cells and we've looked at somatic stem cells. There's actually one more type called induced pluripotent stem cells or IPS cells. It turns out that you can actually introduce a few specific genes into already specialized somatic cells, like muscle cells, and they'll sort of forget what type of cell they are and they'll revert back, they'll be reprogrammed into a pluripotent stem cell just like an embryonic stem cell. And this is a huge discovery. I mean, the technique is still being perfected, but there's a lot of medicinal implications here. For example, IPS cells are basically the core of regenerative medicine, which is a pretty new field of medicine where the goal is to repair damaged tissues in a given person by using stem cells from their own body. So, with IPS cells, each patient can have their own pluripotent stem cell line to theoretically replace any damaged organs with new ones made out of their own cells. So, not only would a patient get the new organ they might need, but there also won't be any immune rejection complications since the cells are their own. So, there's still a ways to go here before this type of medicine is sort of mainstream, but already IPS cells have helped to create the precursors to a few different human organs in labs such as the heart and the liver. Now, before we finish up here, I just want to answer two questions that might have come up for you. So, one, what triggers our stem cells to differentiate? Well, it turns out that in normal situations, right, when the stem cells just hang out, not doing too much, it actually expresses a few different genes that helps to keep it undifferentiated. So, there are few proteins floating around in the cell that prevents other genes from being activated and triggering differentiation. But, when putting certain environments, this regulation can be overridden, and then they can go on and differentiate into a more specialized cell, the type of which depends on what specific little chemical signals are hanging around in the stem cells environment. So, for example, in the bone marrow, there's certain proteins that hang around stem cells and induce some to differentiate into the specific blood cell types. And finally, what's all this stuff you might have heard maybe in the news about cord blood? Well, from cord blood, which is blood taken from the placenta and the umbilical cord after the birth of a baby, you can get lots of multipotent stem cells and sometimes some other stem cells that have been shown to be pluripotent. So, this cord blood used to just be discarded after a baby's birth, but now there's a lot of interest in keeping it because now we know it contains all these stem cells. | ↗ |
| 53 | Interventional Orthopedics of Washington | What Is Regenerative Medicine? | 9951 | 195 | 4 | 63.0 | positive | 0:23 | We have to understand that you know there is regenerative medicine and there is degenerative medicine, right? So what are you practicing if you're practicing something that fights the body You're probably practicing degenerative medicine But if you're cooperating with the body's healing process You're gonna find yourself regenerating your tissues and moving on from your pain problems | ↗ |
| 54 | Hashem Al-Ghaili | Stem Cells and Regenerative Medicine | 17297 | 415 | 24 | 62.9 | negative | 3:19 | Imagine being able to repair and replace human body parts in the same way we do with car parts. This may sound like pure science fiction, but scientists are exploring new medical technologies that could allow them to grow custom-made and ready to use organs. This means diseases like leukemia, Parkinson's, diabetes, heart diseases, and strokes could all be reversed and cured with bioengineered organs. These lab-grown organs would be made from stem cells. So, what are stem cells and where do they come from? Stim cells are special human cells that act as a repair system for our bodies and are able to fix damaged tissues. They are able to develop into many different types of cells, like muscle cells or brain cells. All the cells in our bodies are believed to originate from stem cells. As they mature, they then obtain their functions and become what is scientifically referred to as differentiated cells. Stim cells are divided into two main forms, embryonic stem cells and adult stem cells. Embryonic stem cells are cells found only in very early development and are the precursors to every cell type in the human body. They have an amazing potential to turn into almost any body part. They are also virtually immortal and are able to produce new cells even after months in a petri dish. Some embryonic stem cells used in research today come from unused embryos during an in vitro fertilization procedure. These unused embryos are instead donated to science. Other embryonic stem cells can be created in the lab using genetic reprogramming. Adult stem cells, on the other hand, are rare cells found in the body after its birth and throughout its life. They reside in tissues like the brain, the bone marrow, the blood vessels, the muscles, the liver, and the skin. Adult stem cells wake up when the tissue needs to be repaired because of certain damage or disease. Scientists have been able to harvest stem cells. They were also able to make them from differentiated cells by reprogramming them back to a stem cell state. However, these cells so far are flawed and can only develop into a small number of cell types. Out of the many possibilities to use stem cells, tissue regeneration is the most essential. Currently, the world is facing an organ shortage crisis. In the US alone, more than 100,000 people are on a waiting list for an organ transplant. Being able to bioengineer and grow organs from stem cells would largely help with this problem. At the same time, these organs would be custom made and ready to use. They would be generated from the patient's own stem cells, which would greatly reduce the risk of the body's immune system rejecting the transplant. Scientists could go on to cure heart diseases or diabetes. Special cells made from stem cells could be implanted into the heart or the pancreas where they could replace non-functional cells. Even brain diseases like Alzheimer's or Parkinson's could be cured by repopulating the brain with healthy cells. These scientific achievements are yet to be accomplished for regenerative medicine. The techniques are still far from perfect, but scientists are still researching and working on new ways to harness the power of stem cells. They believe that in a few years from now, regenerative medicine will be available and a preferred method for everybody. What do you think of stem cell research? And what do you imagine the future of stem cell therapy could look like? Share your thoughts in the comments section. | ↗ |
| 55 | UCLA Broad Stem Cell Research Center | Understanding and optimizing stem cell reprogramming | Shan Sabri | 561 | 7 | 2 | 62.2 | positive | 1:04 | [Music] my work aims to better understand the process of stem-cell reprogramming which is the process of creating stem cells from other cells of the body now stem cells could one day be used to help repair the body but this still remains some issues holding them back for being used in the clinical setting now while we've shown that we can alter the fate of a cell we tend to have a small understanding of how to control that fate my goal is to connect the dots between say are starting cells and our end state stem cells so I'm currently writing a computer program to find patterns throughout this process using a new technology that gathers a ton of information from thousands of individual cells now with these patterns we can better understand the reprogramming process and a results will ultimately help researchers better find to their stem cell techniques for more practical uses in a clinical setting [Music] you | ↗ |
| 56 | Medical Appraisals | Stem cell therapy | Medical Appraisals | 19875 | 452 | 9 | 62.0 | positive | 1:01 | Regenerative medicine and stem cell therapy, healing from within. Stem cell therapy, a field that uses the body's ability to heal and regenerate damaged tissues and organs, has the potential to revolutionize healthcare. Stem cells, including embryonic stem cells, eschis, adult stem cells, and induced poropotent stem cells, Ipschase can differentiate into various cell types, offering new treatment options for previously incurable conditions. Stem cell therapy is being explored for various medical conditions, including neurodegenerative diseases, heart disease, diabetes, and spinal cord injuries. However, challenges include the need for rigorous clinical trials, potential immune rejection, and ethical considerations surrounding embryonic stem cell. Advances in gene editing, tissue engineering, and stem cell biology are expected to drive... | ↗ |
| 57 | HeroForce Evolution | Turning Back Time: The Science of Cell Rejuvenation | 1486 | 39 | 1 | 61.5 | positive | 0:32 | As we delve into the realm of cell biology, we encounter this groundbreaking science known as partial cell reprogramming. Our bodies are made up of trillions of cells each with their unique function, but what happens when these cells start to age? Just as the pages of a well-thumb book begin to yellow and fray with time, so too do our cells undergo a process of aging. This cellular aging, or senescence, is a natural part of life, but it's also a key player in the grander theatre of our overall aging process. | ↗ |
| 58 | Miss Estruch | STEM CELLS: Totipotent, pluripotent, multipotent and unipotent. Learn... | 124873 | 1710 | 65 | 61.4 | positive | 9:37 | Hi there and welcome to Learn A Level Biology for free with Misestrick. In this video I'm going to be going through the types of stem cells that you need to know for A Level Biology. So just to recap then on what we mean by a stem cell, the A Level definition, so they are cells which are currently undifferentiated, they also have the ability to continually divide and then become specialised. So you would need to have both of those components in your definition the fact that they can continually divide and they have the ability to become specialised into types of cells. And differentiation which we've got here, the fact that they're undifferentiated cells, that is the process by which stem cells become specialised cells. And we have an example here in the image of a stem cell to show you all the different types or some of the different types of specialised cells it could become. So there's different types of stem cells and that is referring to how many different specialised cells that particular type of stem cell is able to differentiate into. So we're going to go through those different types, totipotent, pleuripotent, multi-potent and unipotent stem cells. So we'll begin with totipotent stem cells and these are the stem cells that can divide into any type of cell in the body. So this is the type of stem cell that you would find in the very very early stages of an embryo. So they're only available for a very limited time and as I said they can divide into or specialised differentiate into any type of body cell. And during development those totipotent cells translate only one part of the DNA and that is how they eventually become specialised. Now in contrast pleuripotent cells these are the stem cells which we can see here in the inner mass of a blastocyst. And a blastocyst is about three to five days after fertilisation that is what the embryo develops into. And the cells around the outside that we can see here in yellow those will go on to make the placenta for the fetus and the blue cells in the middle are the pleuripotent stem cells. And those are the cells that naturally would go on to make the fetus. So if you take out one of those cells they're pleuripotent and they can divide into almost any type of cell and they just can't divide or specialised to form the centre. So these are really useful for research and at the moment they're researching how you could use those types of cells to treat human disorders. Because if those cells can differentiate into any type of stem cell there's the potential that they could be used to create damaged cells or tissues for example replace burnt skin cells or diabetics whose beta cells are not creating insulin which is type one diabetes potentially you could remove those and replace them with healthy beta cells created by pleuripotent stem cells or Parkinson's disease where the neuron to the brain start to break down and they don't produce enough dopamine anymore. So there's a whole range of potential applications. Now I'm emphasising potential because they're not currently used in these treatments because in the research they have found issues and one of those issues is linked to the first part of the definition of stem cells and that is the property that they have the ability to continually divide and what they've found when they've done this research in mice and other animals is that even when they have used stem cells to create new cells to replace damaged ones unfortunately those cells continued to divide to create tumors. Now the other issue is the ethics behind it because in order to get these pleuripotent stem cells you have to create if you want to use it to treat someone you would have to create a zygote which is a clone of the patient you want to treat and we call this therapeutic cloning because you are cloning that individual but you never allow the embryo to go further than the early stages so it's not um reproductive cloning where you are cloning to make a living individual at the end it's therapeutic so you get the embryo or the blastocyst and then you just remove the stem cells you want. So ethically two issues therapeutic cloning but also destroying embryos which some people believe at that stage is already living some people believe there's the potential for life there. So in multi potent and unipotent stem cells then the multi potent ones have the ability to differentiate into a limited number of different cells and you'd find these in the bone marrow for example and the stem cells the adult stem cells found in bone marrow are multi potent because they're able to differentiate into the different blood cells. Now the final one unique potent uni meaning one they can only differentiate into the same type of cell so skin cells can differentiate to make more skin cells or muscle cells will make more muscle cells. So the sources of some of these stem cells then I've gone through some of them as we went but just in summary embryos up to 16 days after fertilization contain the pulmonary potent stem cells so the blastocyst will be able to provide those stem cells from about day four or five up to 16. Umbilical cord also contains some stem cells so sometimes people will keep the blood from the umbilical cord to have a source of multi potent stem cells along with the placenta that also has multi potent stem cells and we said that the bone marrow is a source of multi potent stem cells as well. So the last thing that you need to be aware of is even more recent technologies of how to overcome the some of the issues that we discussed with the pulmonary potent stem cells because pulmonary potent would be the most useful in terms of applications in medicine. However there are pros and cons pros you could potentially treat many diseases cons are and we're just going to focus on here the ethical issues of cloning and then destroying potential life destroying the embryo and that's why scientists came up with this idea of induced pulmonary potent stem cells and often you'll see that shorthanders IPS cells. Now what these are are when you take a somatic cell meaning a body cell from an adult who's giving consent and that could just be a skin cell or the cheek cells so it's easy accessible to get these body cells somatic cells and you can then manipulate the DNA inside of those cells by using appropriate transcription factors and transcription factors you learn about later on topic eight these are molecules which can allow transcription to either occur or not occur for particular genes and in that way if you turn on all the genes again in a cell they are now no longer a specialized cell and you've now induced that body cell to become pulmonary potent again and that cell can then be used potentially for treatments and in this way we've overcome the ethical issues of there's no cloning involved and no embryos are destroyed. So how they do this again I said a little bit about this so the IPS cells are created from the adult unipotent cells once you've then switched back on all the genes we call that return to the state of pulmonary potency and that is using the transcriptional factors so once you've done that these induced pulmonary potent stem cells behave pretty much exactly the same as the pulmonary potent cells from a blaster cyst. They have also shown cell for new properties and they can divide indefinitely to give limitless supplies so you wouldn't have to go through this whole process every time you can allow them to divide and then you can keep a source of them for that particular patient. So that is it for our stem cells types of stem cells and applications. If you found it helpful please give it a thumbs up and make sure you subscribe to keep up to date with all the latest videos. | ↗ |
| 59 | Ways2Well | The vision was clear. Build a place people want to walk into. That's o... | 234 | 10 | | 61.3 | | 1:26 | One of my favorite things is when people come to Austin and they see what we call the mother ship. And where it came from was honestly, as a little kid, I was terrified of the dentist. And my mom found a dentist's office that when I would go there, he had toys, he had a basketball goal. He had like a toy box with ninja turtles. And for me, it made the dentist fun. And when I look at medical practices or my years in the operating room, everything was so sterile and white and cold and intimidating. And we're not here to intimidate or to lead from an arrogant standpoint. We're here to be a partner on your journey. And part of being a partner to me is making healthcare fun again. Like let's make your healthcare journey fun. Let's make it approachable. And so I've tried to incorporate so many hints from my youth like embrace the nostalgia and embrace movies, make the clinic fun, make it where this is a place people want to be, where people want to come for treatments. And I think we don't have a pretty good job of that. Most people come in and their minds blown about what we've built here. But separate from that, like even the coolest building in the world would be nothing without the right staff. And the staff at this company, un-be-leabable team. And anybody who ever comes to this building will have a world-class experience because the team, the experience, the knowledge, and the passion. These people care. | ↗ |
| 60 | KPIX | CBS NEWS BAY AREA | Breakthrough Stem Cell Treatment Gives Stroke Victims Stunning Recover... | 128784 | 1110 | 176 | 60.8 | negative | 2:38 | WE HAVE SOME REMARKABLE VIDEO TO SHOW YOU TONIGHT. STROKE VICTIMS.. MAKING INCREDIBLE PROGRESS... LITERALLY OVERNIGHT. THANKS TO A NEW KIND OF TREATMENT AT STANFORD. EMILY TURNER IS HERE WITH A STORY YOU'LL SEE ONLY ON FIVE. IT WAS A SMALL CLINICAL TRIAL AT STANFORD, THAT INVOLVED AN EXPERIMENTAL TREATMENT WITH SPECIAL STEM CELLS. THE DOCTORS ARE STUNNED AND THE PATIENTS - OVERJOYED. FIVE YEARS AGO, SONIA COONTZ SUFFERED A STROKE - THAT SEVERELY DAMAGED HER BRAIN, This is Sonia's stroke IT PARTIALLY PARALYZED SONIA ON HER RIGHT SIDE, AND SHE COULD BARELY SPEAK. "Her speech was not very understandable She couldn't order food or communicate well" TWO YEARS LATER, SONIA COULD STILL HARDLY LIFT HER ARM. BUT JUST ONE DAY AFTER AN EXPERIMENTAL TREATMENT - - "Oh my gosh " SONIA COULD LIFT HER ARM OVER HER HEAD- (PAUSE) AND MOVE IT TO THE SIDE -(PAUSE) AND ALS0 TO THE FRONT. AND HER WORDS BEGAN TO FLOW "I woke up and immediately I could speak better " "she's what we call one of our miracle patients. DOCTOR GARY STEINBERG, CHAIR OF NEUROSURGERY AT STANFORD, LED THE SMALL CLINICAL TRIAL. EIGHTEEN CHRONIC STROKE PATIENTS WERE INVOLVED. TWELVE CAME TO STANFORD - - INCLUDING SONIA "i was very excited i think i started to cry" . IN THE TRIAL, STEINBERG DRILLED A TINY HOLE INTO THE PATIENT'S SKULL AND USING A VERY FINE NEEDLE, INJECTED MODIFIED HUMAN ADULT STEM CELLS AROUND THE STROKE. we put them around the stroke and that where they do their thing to recover the function. THESE STEM CELLS ARE CREATED BY "SAN BIO" - A BIOTECH COMPANY LOCATED IN MOUNTAIN VIEW. It's very exciting SCIENTISTS HERE DERIVED THEM FROM THE BONE MARROW OF TWO ADULT DONORS, AND THEN TWEAKED THEM. THESE CELLS DON'T SURVIVE FOR LONG AFTER TRANSPLANTATION. BUT THEY APPEAR TO TRIGGER A PATIENT'S DAMAGED BRAIN TO BEGIN TO HEAL ITSELF. "we think that transplanting the stem cells is jumpstarting the circutis. " HERE'S ANOTHER STROKE PATIENT JUST BEFORE SURGERY.. AND HERE SHE IS JUST DAYS AFTER RECEIVING THE STEM CELL TREATMENT. AS FOR SONIA, HER LIFE IS BACK ON TRACK. SHE'S NOW MARRIED AND PREGNANT WITH HER FIRST CHILD "it's a boy yeah.. (laughs)" NOT ALL OF THE PATIENTS, BUT MOST OF THEM IN THE STUDY SAW A OF THEM IN THE STUDY SAW A BENEFIT THAT HAS LASTED. BUT STEINBERG IS CAUTIOUS AND WANTS TO REPLICATE THESE FINDINGS IN A MUCH LARGER TRIAL. THAT STUDY IS NOW ENROLLING PARTICIPANTS. THESE RESULTS WERE PUBLISHED THIS AFTERNOON IN THE JOURNAL, STROKE. FOR MORE INFORMATION, GO TO KPIX DOT COM | ↗ |
| 61 | Thermo Fisher Scientific | How to culture pluripotent stem cells in suspension: Passaging of PSC ... | 72358 | 229 | 8 | 60.8 | positive | 4:20 | Passaging of stem scale PSC suspension cultures. Passaging of the PSC's feroids is recommended when they approach 400 micro-muller in size. To avoid the formation of an acrotic core and loss of pluripotency. When using stem scale PSC suspension medium, this generally occurs after 4 to 5 days of growth. To passage the stem scale PSC suspension cultures, you will need. Stimpro acute cell dissociation reagent completes stem scale medium, Y27632 compound, and a CO2 resistant shaker. When PSC's feroids are readily be passaged, prepare the desired number of suspension culture vessels as described earlier. To passage the PSC's feroids, start by swirling the culture vessel slowly in a circular motion to gather spheroids to the center of the well. Collect the spheroids by pipetting or pouring the spheroid containing medium into a 50-millilater conical tube. Watch the walls of the emptied culture vessels with stem scale medium to collect any spheroids that may have been left behind. Collected spheroids should be centrifuged at 200 times gravity for 4 minutes. After centrifugation, aspirate the spent stem scale PSC suspension medium. Add the recommended volume of pre-warmed stem pro acute cell dissociation reagent. Do not use a P1000 pipet to chriterate the spheroid pellet as this may negatively impact cell viability. Allow the spheroids to dissociate in a 37-degree Celsius water bath for 10-15 minutes. During the 10-15 minutes, periodically mix the spheroids by flicking or gently shaking the tube at intermittent intervals. The cell suspension will become cloudy as more spheroids have dissociated into single cells. After 10-15 minutes of incubation and stem pro acute cell dissociation reagent, triturate the cell suspension 5-7 times using a P1000 micro pipet to further break up the spheroids into single cells or small clusters. Once the spheroids have completely dissociated add 3 milliliters of stem scale medium per 1 milliliter of gupco stem pro acutease. To inactivate the dissociation reagent and mix by gentle inversion, the single cell suspension should then be centrifuged and cells resuspended in fresh stem scale PSC suspension medium. Supplement of a 10-micromolar of Y27632. Similar to initiating the PSC suspension cultures count and seed 100 to 150,000 cells per milliliter of medium. In a new non-tition culture treated vessel, before placing a vessel on the CO2 resistant orbital shaker in the incubator. More instructional videos are available but cover the entire stem scale PSC suspension workflow. To find out more, visit thermofisher.com slash stem scale. | ↗ |
| 62 | UF Health | What is Regenerative Medicine? | 17616 | 257 | 13 | 60.7 | positive | 2:30 | Regenerative medicine is the use of various biological factors, including particularly cells and genes, to help repair, rescue, and ultimately regenerate various organs and tissues in the body, so that we can combat the opposite of regenerative medicine, which is degenerative disease. So often with a variety of circumstances, often with aging, many of the organs and systems of the body begin to degenerate, and unfortunately we have no medical therapy for several of those kinds of degenerative diseases. The technologies and methods used in regenerative medicine include several parts. We have to obtain cells to work with, we have to grow those cells, and then we have to deliver those cells in an appropriate way, all of which are involved in what you might call the overall process of regenerative medicine therapy. And for the last 15 years and more, I and my group have been studying the cells that one can get out of the blood vessels in the fat, and these adipose derived or fat derived stem cells are particularly potent and helpful to conquer, we think, a number of degenerative diseases. One of my particular interests is to actually bring new therapies forward into patients. And thankfully we've been able to do that in some instances. We have been able to license technologies out of our laboratory over the years. And one of the technologies I'm very grateful to note has actually made its way to be helpful in about 9 million patients. So we would like to continue to work with multiple collaborators to bring new technologies and approaches forward to help with diseases in the area of degeneration using technologies of regenerative medicine. The goal of the collaborative process that the University of Florida Center for Regenerative Medicine will really live on is working together with all the multiple departments involved to address particular target disease areas that currently don't have a great medical solution. We will use approaches of cell therapy, approaches of gene therapy, and other biological tools to address those diseases, department by department, often bringing together people from various disciplines in order to work together to solve other disease processes that may learn one from the other. | ↗ |
| 63 | University of California Television (UCTV) | Making Pluripotent Stem Cells | 82814 | 1326 | 22 | 60.6 | positive | 2:22 | Pluripotent stem cells are critically important to the work of the UC San Diego stem cell program. They allow the motri lab to grow neurons with neurological defects, and Carl Wollins lab to grow retinal cells with eye diseases so they can try to find cures. But how are they made? 2012 Nobel Laureate Shinya Yamanaka discovered that by reactivating only four specific genes and adult cells, they would become pluripotent, which means they can be reprogrammed to make any tissue in the body. Like the neural and retinal cells, the motri and Wollin lab use, as well as many other types of cells used to study or treat diseases. Dallas and Wollin lab can take cells from inside your mouth and provide them with the genes that Yamanaka discovered. The genes are introduced into the cells using viruses that can deliver the genes in a way similar to how a virus causes infection in a cell. The genes cause the cells to produce specific proteins. These proteins enter the nucleus and act on the cells DNA. This causes the cells DNA to convert the cells into pluripotent stem cells. These are called induced pluripotent stem cells, or IPSCs. The lab then carefully cultures the IPSCs, which grow in a thin layer, constantly caring for them to make sure they grow well. One reason IPSCs are so useful and important is that since they come from adult cells, they carry the genetics of the donor. This allows the motri, Wollin, and other labs to capture the genomes of real disorders, so they can work with the cells to find real cures, which the UC San Diego stem cell program is doing right now. | ↗ |
| 64 | Serious Science | Induced pluripotent stem cells - Rudolf Jaenisch | 16695 | 269 | 12 | 60.6 | positive | 11:45 | In use to report stem cells have a long history. What I learned at school was development is irreversible. So once a cell develops to a liver, it's a liver. It cannot become a brain. It cannot become an embryo. It's irreversible. This concept was shaken. Half a century ago by the seminal nuclear transplantation experiments of John Gerden. So what he did, he took the nucleus of a somatic cell, a cell of the intestine, and put the nucleus into the egg of a frog. And he reprogrammed, it wasn't called this, then, he reprogrammed this nucleus to become a whole frog. So development was not irreversible. So then in the 90s, when embryonic stem cells were discovered, nuclear cloning and stem cells were put together to the concept of a therapeutic cloning, which means you could make a embryonic stem cell from a patient. From a patient who want to generate cells for to a therapy. Like if you have a blood disease and you have sickle cell anemia, then you want to treat this with what's called autologous cells, autologous bone cells, which are not rejected. They have to come from the patient. How would you make that? You can't. But then you take the skin cells from this patient and reprogram it in the egg and the human egg. And then you get an embryonic stem cell. From this you can make a blood stem cell. That can be transplanted. Okay. The problem was for human consumption was human eggs are difficult to get and nuclear transfer in humans hasn't worked yet. So the problem was how do you do the reprogramming without eggs? And this was the invention of IPS cells, induced pluripotent stem cells. So what was discovered in 2006 by Yamannaka was you can use a few factors. Prescription factors. Put them into a fibroblast in a skin cell and induce this cell to undergo a reprogramming to a pluripotent state, which means these skin cells which normally are there to make hair and pigment but not brain and liver. There would become no pluripotent and these pluripotent cells could now make brain, liver, hair and skin, everything. So this was a major breakthrough because you could use now these cells potentially for studying diseases. I'll come to that later. You can study human development and it has an enormous scientific implication because you suddenly the concept of irreversibly of differentiation of being a liver cell, a brain cell or skin cell was shattered. It was not irreversible. It was fully reversible. There is nothing like an irreversible cell state. And indeed, following these discoveries of IPS cells, we are now able to convert fibroblast to an IPS cell and then the IPS cell to a liver cell or directly take the fibroblast and make directly a liver. It's called trans differentiation. So suddenly we had to realize things are much more flexible. So what is behind that? Well what's behind that is that first of all, which was in the original GERD experiment, nuclear transfer and frogs was the question, what's the difference between a liver cell and the brain cell? So it was clear liver cells would express different genes and brain cells. One way to achieve this would be you just delete the rid of the brain genes in the liver and the liver genes in the brain. So there would be genetic differences between brain and liver cells. If that was a case, nuclear transplantation should never have worked. Because it worked, it was clear this was not the case. So that was established. The IPS cells tell you know, well, it works pretty easy. You just have to culture the cells in a certain way, treat them in a certain way and you convert a skin cell to a liver cell and a skin cell to a brain cell. So that's really, so how does it work? That's of course great scientific interest. And what comes out, no, what sort of crystallizes is what we call epigenetic. It's the epigenetic state of the genes. So the genes are there in the liver, but they're not expressed. They're not expressed because they are packaged into chromatin, into histones. The DNA is modified, we call it epigenetic modification. So the genes are silent. The same genes, let's say brain genes, they're not silent in the brain because they're these genes are in a different epigenetic state and they can be expressed. So now we are able to switch that. Switch the different types of pattern of epigenetic modifications where cell types differ to one to each other. And I think the IPS, the IPS approach, led the way where we learned how to do that. And I could go into what one has to do, it becomes clear and clear, although there's much to learn. So I think it has a major developmental dimension, the IPS cells to learn what's the difference between two types of cells. It gives us the ability to convert one cell type to the other. And it will have, I think, enormous potential to study human diseases and potentially to call for therapies. So there are many, many issues here. So one issue is what is a good IPS cell? Because very easy to make bad ones. So what is a good one? What are the criteria? So in mouse, we work lots with mouse. That is rather easy because these cells of their good can make mice. So you take these skin cells, make an IPS or make a mouse. That's a pretty good system, right? I mean, imagine a skin cell makes a complex organism with eyes and a heart and hair. That's pretty amazing, right? If you think about it. Now, when you think about human IPS cells, you don't have that test. You cannot take human IPS cells and inject them into a human early embryo and make it what we call a camera. That's not allowed and not possible. And of course, that would be an nonsense experiment. So we have to rely on different criteria. And there is a lot of discussion and I think that's not resolved. For example, the gold standard, I embryonic stem cells, which come from an embryo. In mouse from a mouse embryo, a human from a human embryo. IPS cells come with this conversion process from a let's say skin cell or some other somatic cell. And it's clear there are differences. In mouse, we know these differences. In humans, we don't know. What is a gold standard? What do we have to try to aim to get? And so these are very important questions, which are not resolved at this point. And there comes together, they have to be analyzed by epigenetic confirmation, by genetic, by all sorts of means, and biologically. So I think there are many, many questions which have to be resolved. I think the biggest problem now, or the most unresolved problem, is how do you make specific cell types from an IPS cell? So the IPS cell can grow forever there in model, but you want to make mature liver cells, mature beta cells of the pancreas, for example, to study diabetes or neurons. And that's at the moment is still a problem. We want to learn how best to differentiate these cells to mature functional cells, which could be used to study the function of a liver cell, but also to provide cells, let's say, for therapy or liver disease. These are very important issues, they are really largely unresolved. I think we're getting, now, the methods in hand to begin to resolve those and to answer those. But I think that's a very active, it remains a very active topic of research, where we need progress. And the question really would be, can you make organs? Now, IPS cells or M-Ringstem cells are able to make organs in the embryo, in the context of developing embryo, sure. But that's not what we can do with human cells. So with human cells, we can ask the question, can you make a liver in the patronage? And the answer is no. You can make liver cells, but not a liver. You can make heart cells, but not a heart. It's a very complex organ like a heart, which only can develop in an embryo when all sorts of influence and all sorts of signals coming from different parts. So this is not possible, although people begin to try to use by engineering to make simple organs, they put a scaffold into this and make maybe an organ like a nurse of a ghost or a truck here, where you see cells on it and that's possible. But these are simple structures, of course. But a very complex structure like a kidney or a heart that is really at the moment not possible. But I don't think we need that for this technology to be highly useful for learning something about how organs function and how specific cells function. The future for this will be to resolve the technical issues which I outlined. Some of them was differentiation. So when we were, we go back ten years, when we had only nuclear transplantation to make this patient specific cells, for example, the biggest issue was to do it without cells, without eggs, and that's what's resolved. That was the biggest issue which hold back the field. This is resolved. I think these cells, now I think this is resolved. So I think we will have now getting into the more technical issues like differentiation and this will be probably resolved. There are so many people working on it within five to ten years, I think. Then we will have a very defined system where we can predict, you do this and this is the outcome and that's what you would like to have. | ↗ |
| 65 | TED-Ed | What are stem cells? - Craig A. Kohn | 2232359 | 27273 | 842 | 60.3 | positive | 4:11 | Imagine two people are listening to music. What are the odds that they are listening to the exact same playlist? Probably pretty low. After all, everyone has very different tastes in music. Now, what are the odds that your body will need the exact same medical care and treatment as another person's body? Even lower. As we go through our lives, each of us will have very different needs for our own health care. Scientists and doctors are constantly researching ways to make medicine more personalized. One way they are doing this is by researching stem cells. Stem cells are cells that are undifferentiated, meaning they do not have a specific job or function. While skin cells protect your body, muscle cells contract and nerve cells send signals, stem cells do not have any specific structures or functions. Stem cells do have the potential to become all other kinds of cells in your body. Your body uses stem cells to replace worn-out cells when they die. For example, you completely replace the lining of your intestines every four days. Stem cells beneath the lining of your intestines replace these cells as they wear out. It's hope that stem cells can be used to create a very special kind of personalized medicine in which we could replace your own body parts with, well, your own body parts. Stem cell researchers are working hard to find ways in which to use stem cells to create new tissue to replace the parts of organs that are damaged by injury or disease. Using stem cells to replace damaged bodily tissue is called regenerative medicine. For example, scientists currently use stem cells to treat patients with blood diseases such as leukemia. Leukemia is a form of cancer that affects your bone marrow. Bone marrow is the spongy tissue inside your bones where your blood cells are created. In leukemia, some of the cells inside your bone marrow grow uncontrollably, crowding out the healthy stem cells that form your blood cells. Some leukemia patients can receive a stem cell transplant. These new stem cells will create the blood cells needed by the patient's body. There are actually multiple kinds of stem cells that scientists can use for medical treatments and research. Adult stem cells or tissue specific stem cells are found in small numbers in most of your body's tissues. Tissue specific stem cells replace the existing cells in your organs as they wear out and die. Breonic stem cells are created from leftover embryos that are willingly donated by patients from fertility clinics. Unlike tissue specific stem cells, embryonic stem cells are pleuripotent. This means that they can be grown into any kind of tissue in the body. A third kind of stem cells is called induced pleuripotent stem cells. These are regular skin, fat, liver, or other cells that scientists have changed to behave like embryonic stem cells. Like embryonic stem cells, they too can become any kind of cell in the body. While scientists and doctors hope to use all of these kinds of stem cells to create new tissue to heal your body, they can also use stem cells to help understand how the body works. Scientists can watch stem cells develop into tissue to understand the mechanisms that the body uses to create new tissue in a controlled and regulated way. Scientists hope that with more research, they can not only develop specialized medicine that is specific to your body, but also better understand how your body functions, both when it's healthy and when it's not. | ↗ |
| 66 | Amoeba Sisters | How Cells Become Specialized [Featuring Stem Cells] | 1292547 | 10536 | 318 | 60.2 | positive | 6:51 | We've mentioned a lot about specialized cells. Specialized plant cells, specialized animal cells, so many kinds of specialized cells, it's going to get a bit crowded here. But have you ever wondered, how do they get specialized? How does a neuron or a muscle cell in your body have the structure and function they have? I mean, can you imagine if they had a switch jobs for a day? That wouldn't go so well. They're so specialized for the function they perform. Well this video is going to talk about how cells differentiate into other cells, which basically means how cells become specialized. Remember that many multicellular organisms, like a plant, or you, well these organisms come from a fertilized egg cell. Let's take a look at a human fertilized egg, otherwise known as a zygote. Well, that's zygote divides to make more cells. And more cells? Oh look, it's a more yellow. And more cells? Oh look, it's a blastocyst now. You know the problem is, if the cells just keep dividing, if you remember from our mitosis video, that makes identical cells. Well, that's great for growth, and so dividing is definitely going to happen, but that alone is not going to result in different specialized cells with different specialized functions. There's something else that will be happening for that. So let's take a look at that in a bit of detail. We're going to pause here, the blastocyst. Notice it has stem cells, and these stem cells, they're amazing. See, they're not differentiated yet. They're not specialized. They're like blank slates. They don't have a special structure. They don't have a special job. They can become any type of body cell. Now, we'll reminder about body cells in your body. They all, with a few exceptions, contain all of your DNA. So neurons and muscle cells in your body, they don't have different DNA. They use different parts of your DNA. Genes are regulated, which means the genes can be turned on and off. It's important to understand, because that's a big part of how these stem cells are going to specialize. Stem cells will activate certain genes in the process of differentiating into different types of cells. Transcription factors are major key players here. They're typically, but not always, proteins, and they determine which areas of the DNA code will get transcribed into mRNA. Now, that mRNA can eventually be used to make specific proteins that can impact what a cell is going to look like and what a cell is going to do. That means transcription factors have a major role in determining which genes are expressed in a cell. Because a cell that's going to become a skin cell, that's going to have different areas of genes expressed than a cell that's going to become a stomach cell. There are both internal and external cues for stem cells, which can involve these transcription factors. Examples? Okay, an example of an internal cue could be transcription factors present in the cytoplasm of the original starting zygote cell, which will eventually be present in the cells that come from it. Now, the specific location of the stem cell within the developing embryo can matter, because the transcription factors available in different areas of the developing embryo can differ in quantity and type, which could impact what a stem cell differentiates into. External cues could involve cells signaling from other cells next to it. External cues can even be environmental effects like temperature. There's still a lot of research in this area, and we can't wait to see what scientists discover about this in the next decade. So stem cells are the unspecialized, undifferentiated cells that can become other cells in your body. But not all stem cells are found in a developing embryo. Stem cells can also be found in your body as well, like your muscle, skin, liver, bone marrow, just to name a few. These are often called somatic stem cells. To give some relevance to this, it's likely you've heard of bone marrow transplants before. Well, bone marrow transplants actually involve transplanting a portion of healthy bone marrow, which does contain bone marrow stem cells, with the idea that those donors stem cells can help regenerate different types of blood cells since bone marrow is like a blood cell making machine. It contains stem cells that differentiate into different types of blood cells. Many, but not all, of the somatic stem cells that are found in your body are considered to be multipotent. That means they can become many types of cells. But not as many as the embryonic stem cells. So after talking about these stem cells, why the heavy focus on them right now in research? Well, one reason, of many, is that these cells have the ability to differentiate into other cells, and therefore they could be used to help regenerate organs or tissues that are damaged from a disease or an accident. There are two important issues to consider, however. One is the ethical issue, especially if considering embryonic stem cells. The ethical issue is significant because the extraction of embryonic stem cells results in the demise of the embryo. One point consistently debated is the potential benefits offered in embryonic stem cell research, versus the onset of personhood of human embryos. A second issue is that organ or tissue developed from stem cells that didn't originate from that person will carry the risk of organ or tissue rejection, possibly similar to what you could get with donated organs or tissue. But here's something promising. Some research shows that somatic stem cells from your own body may actually be able to develop into more types of cells than what people first thought. In fact, it was discovered that some somatic stem cells can be induced to go back into a pluripotent state. They're called induced pluripotent stem cells. That means a person's own somatic stem cells from their own body could potentially be induced into a pluripotent state with the potential that they could differentiate into tissues or organs that the person may need. Theoretically, this could be an alternative to waiting for an organ or tissue donor, as well as lower the chances for organ tissue rejection, since the organ or tissue would have originated from the person's own cells. We encourage you to keep up with the topic of stem cells. To stay educated on this topic, the understanding of these undifferentiated cells is likely to advance in the near future. Well, that's it for the Meeva Sisters, and we remind you to stay curious. | ↗ |
| 67 | Nucleus Medical Media | Stem Cells | 1232636 | 12351 | 272 | 60.1 | positive | 5:03 | The human body contains organs such as bones, the brain, heart, and reproduction. The basic cells that give rise to all of the different cells in these organs are called stem cells. One type of stem cell is an egg cell from a woman that has been fertilized by a sperm from a man. This single cell, called a zygote, is the first cell in a developing human being. It's also called a totipotent stem cell because it can form any type of cell in the body, as well as the umbilical cord and placenta. After a zygote has divided a few times, it becomes an early stage embryo called a blastocyst. Embryonic stem cells come from the cells inside the blastocyst. Embryonic stem cells are pluripotent. This means they can form any cell in the body, but not the cells in the umbilical cord or placenta. In the lab, embryonic stem cells are donated from leftover embryos created during in vitro fertilization. In vitro fertilization is a procedure to help a woman become pregnant. Another type of stem cell is an adult stem cell. Small groups of these cells are found in some organs such as the skin, after birth, and into adulthood. Adult stem cells are multipotent. This means they can only become a few different cell types related to the organ where they're found. For example, the skin contains a small number of adult stem cells that can divide to create new skin adult stem cells. Or they can become more specialized skin cells to replace those that are lost due to cell aging or damage. In the lab, scientists can now induce or cause a regular body cell such as a skin cell to change into a pluripotent stem cell. Like embryonic stem cells, these induced pluripotent stem cells can become any type of cell in the body. Scientists study stem cells to learn how and why they become many different types of cells. In the future, these cells may be used to regrow tissues and organs that have been damaged by injury or disease. Stem cell therapy is a procedure that uses stem cells to treat a disease or condition. Currently, stem cell therapy only treats diseases and cancers of the blood. In leukemia, for example, the patient's bone marrow makes many abnormal white blood cells that can't do their job to fight infection. Over time, these abnormal cells crowd out the production of healthy white blood cells. In stem cell therapy for leukemia, called hematopoetic stem cell transplantation, a doctor will take a sample of blood or bone marrow from the patient or a donor. In some cases, donor blood may come from a baby's umbilical cord after it's born. These tissue samples contain healthy hematopoetic or blood forming stem cells. Then, doctors will give the patient chemotherapy drugs or use radiation to kill the abnormal white blood cells and their stem cells. Once the abnormal cells are gone, the doctor will transplant the healthy hematopoetic stem cells from the tissue samples into the patient. These healthy stem cells will make new blood cells, including normal white blood cells, which will allow the body to fight off infections. | ↗ |
| 68 | Science Channel | How It's Made: Regenerative Medicine | 237445 | 2440 | 81 | 60.1 | positive | 5:25 | When parts of the human body break down or are damaged, options are limited. Scientists are working on providing replacement parts on demand, like fingers, ears, and bladders. Laboratory engineered bladders have already been successfully implanted in humans. The stuff of science fiction may soon be a reality. They begin with a mold, a finger mold on the right, and an ear on the left. These molds could be made of synthetic polymers or natural materials such as collagen. Scientists will grow real cells on the molds. To obtain those cells, a scientist first extracts a small piece of cartilage, which is a type of connective tissue in the body. She chops it into little bits. She transfers the minced cartilage to a test tube, partially filled with a special enzyme. This enzyme dissolves tissue, leaving only the cartilage cells. She then places the test tube in a centrifuge for a high speed spin. This causes the cartilage cells to separate from the enzyme solution and settle on the bottom. She siphons off the liquid and the tiny cells remain in the test tube. Next, she adds a red liquid. It's a culture medium. It will act as a fertilizer to stimulate cell growth. Once for a to a petri dish, she switches the mix to dispense the cells. Then it's into an incubator, warmed to 98.6 degrees Fahrenheit, body temperature. It's the perfect environment to spur more cell growth. Meanwhile, a computer-controlled machine builds the mold of the ear. It layers synthetic polymer to produce an authentic-looking shape. This process takes about five hours. In the meantime, the microscopic cells have multiplied 20 times. The scientists drips them onto the completed mold, where they continue to grow. In the future, cell-covered ear molds could be implanted under a patient's skin. Cartilage would form, and the body would accept the part as its own. Other scientists are working on growing blood vessels and heart valves. They start by extracting a type of stem cell from human blood. The researcher first fills a test tube with the clear, high-density solution. He adds diluted blood to the clear solution. Almost instantly, the different components of the blood begin to separate. The heavier red blood cells plummet, and the lighter stem cells rise to the top of the test tube. A spin in the centrifuge leaves the components visibly separated, allowing scientists to retrieve the desired cells. They'll convert them to endothelial cells, which line the inside of blood vessels and heart valves. In the meantime, they construct the blood vessel mold. The scientist adds solvent to liquid collagen, causing it to instantly dissolve. He adds little white beads, their synthetic polymers, and they liquefy over a period of about an hour. They spray the collagen concoction onto a rod that spins, as a carriage moves it to and fro for even coverage. The collagen and polymer mixture quickly solidifies around the rod. The scientist slides off the now hardened biomaterial. He now has a mold for shaping a human blood vessel. He coats the mold with a microscopic endothelial cells, which by now have grown and multiplied. He then pumps fluid through it to simulate blood flow. This conditions the cells to go with the flow and collectively operate as a real blood vessel. To grow a heart valve, they don't actually build a mold. They use a real valve from a pig. The scientist plunges the pig valve into a container filled with a mild detergent. It goes into a machine that shakes it up. The agitation helps scrub off the cells, leaving only the valve skeleton. He saturates the valve skeleton with human cells, where they grow and thrive. The research team then pumps fluid through the valve, just like they did with the blood vessel. This trains the cells to do the work they would need to do in the human body. Even Dr. Frankenstein would be impressed. | ↗ |
| 69 | Mannatech | Dr Steve Nugent Explains Immunomodulation PT | 91 | 5 | | 59.9 | | 1:04 | True ACE Manning that we've trademarked as Manipul is the single most important immunomodulatory ingredient that I've seen in any product in my entire career. Immunomodulation. What does that mean? Well if you think about, let's imagine that my left hand is, is normal immune function. Normal is what you want. So if the immune system needs to get a little bit stronger, then it will modulate up to normal. If for some reason it's gone overactive, it needs to modulate down to normal. So what you want is immunomodulation. That's the key. That should be everyone's goal. I've never seen anything better for immunomodulatory effect than Manatex Manipul, which is the only true ACE Manning in the world. | ↗ |
| 70 | The Explorer's Guide to Biology | Induced Pluripotent Stem Cells (iPSCs) | 10801 | 145 | 1 | 59.8 | positive | 2:18 | Multisolar organisms, such as a cat, have many billions of cells. These include somatic cells, shown here in orange, and stem cells, shown here in green. Somatic cells from the Greek, Soma, or body make up the body of an organism and are committed to specific cell fate. For example, the skin cells can divide to make more skin cells, but not muscle cells or other types of cells. In contrast, pluripotence themselves plurimines several while polimines to be able can make any kind of cell. For example, both skin and muscle cells. Pluripotence themselves exist as part of normal development embryos, but they do not exist in adults. So is it possible to give adults pluripotence themselves? In 2012, Dr. Xinyaya Manaka won the Nobel Prize for discovering that adding the four genes, MIC, OCT3 or IV, SOX2 and KLF4 into somatic cells leads to induced pluripotence themselves, or IPSCs. Why is this so important medicine? Since IPSCs can grow continuously and give rise to every other cell type in the body, it can be used to replace damaged cells and tissues, such as in a case of muscle damage, contributing to the feel of regenerative medicine. Since IPSCs can be derived from adult somatic cells, each individual patient could have their own stem cell line for organ transplants, for example to get a new liver. In addition, IPSCs can be used to test what specific treatment works best for individual patients, contributing to the feel of personalized medicine. | ↗ |
| 71 | TRT World | Revolutionary stem cell treatment is curing severe type 1 diabetes | 30270 | 723 | 17 | 59.7 | negative | 2:00 | A revolutionary stem cell treatment trial is showing positive results in curing severe type 1 diabetes. A team from the University of Toronto used stem cells to grow new eyelet cells and administered them to 12 patients. After 12 months of receiving the Zimila cell stem cell therapy, 10 out of 12 patients no longer needed to take any insulin shots. But how does it work? Type 1 diabetes means that a person's body can't create insulin, a hormone that controls sugar levels in blood. Without insulin, sugar builds up and can hurt a person's organs. But too much insulin can be dangerous, too. Normally, special cells in your pancreas called eyelet cells create insulin. But in patients with type 1 diabetes, these cells are damaged. The new treatment uses stem cell infusions to help the pancreas produce insulin again. The team used eyelet cells derived from human stem cells. These cells produced insulin safely in the body, helping patients rely less on costly insulin injections. By around 6 months after receiving the new eyelet cells, most patients didn't require any insulin shots at all. And their problems with low blood sugar disappeared within the first 90 days of treatment. However, because a special medication needs to be taken alongside the treatment to protect the new cells, some patients suffered side effects like weaker kidneys. Two patients died, but not as a result of the stem cell treatment. One succumbed to an infection after surgery, and the other died due to an unrelated health issue. The downside is that patients must take the medication continuously, which raises the chance of infections. The trial will now look at ironing out issues before it can seek approval and start changing the lives of 9.5 million people with type 1 diabetes around the world. | ↗ |
| 72 | SF Business Times | Shinya Yamanaka explains induced pluripotent stem cells | 47932 | 347 | 29 | 59.6 | positive | 2:17 | Great. So I guess first of all if you can explain in a understandable way as somewhat scientific but also understandable for my readers and viewers what are induced chloropotent stem cells. So can I say just IPS cells? Yes, so IPS cells are very similar to ES cells and Bureonic stem cells but it's not from Enriots but from skin cells or blood cells, body cells. So we don't have to use Enriots. Instead we can make IPS cells from patients on cells and from IPS cells we can make variety of cells. Virtually all types of cells that exist in a body like heart cells, brain cells, muscle cells. Those cells we can use in many medical applications such as drug discovery and also regenerating medicine. So that's but IPS cells are. How are those developed? How did you come across this in the world? So we knew we should be able to make IPS cells from skin cells. We can we should be able to convert skin cells into back into embryonic state. You know, about a very famous sheep, right? So she was born by a re-programming of somatic cells back into the embryonic state. So from that experiment we learned that we should be able to convert somatic cells back into... | ↗ |
| 73 | The Jackson Laboratory | What are induced pluripotent stem cells? | 5108 | 114 | 7 | 59.3 | positive | 0:39 | An induced play-pote stem cell is an artificially derived stem cell that is made by essentially reprogramming another cell of the body, for example, a fibroblaster, a blood cell. The Nobel Prize winning technology, the ability to express a small number of factors in the cell and essentially revert that cell back to its original stem cell form. So now it has these two abilities, I mentioned, both self-renew, which is useful for us in the lab when we want to continuously grow these cells. And then the ability, given the right biological cues, to differentiate into another cell type, like a muscle cell or a neural cell or something like that. | ↗ |
| 74 | Regen Report | Stem Cell Pioneers: iPSC Discovery, Potential, and Manufacturing, Inte... | 107 | 7 | 2 | 59.3 | positive | 36:26 | No transcript | ↗ |
| 75 | TEDx Talks | Promises and Dangers of Stem Cell Therapies | Daniel Kota | TEDxBrooki... | 603261 | 5616 | 538 | 59.1 | negative | 12:39 | I'm here to tell you that stem cells are probably coming to a clinic near you, but that's not necessarily a good thing. You see, whenever people find out I'm a scientist, they usually ask me, how's this whole stem cell thing going? And I'll be honest with you, I, for the longest time, I had no idea how to answer that question. You see, I'm from Brazil, as you can tell. And you, and you, and you, and you're, in Brazil, when you tell people your scientists, there's, there's no follow up question. There's only this look on people's faces, you know? It's a mixture of sorrow, concern, a little bit of disappointment, you know? It is really the look of a father whose daughter just brought a boyfriend home and is going, of all the choices out there. I mean, that's what you decided to go with. And, and yes, and so I stuck with science. And I was really fortunate to have the opportunity to come to this great country. And for the past 10 years, I have immersed myself in stem cell research. Now, the, but in here, people are really interested in science, right? And like everything else nowadays, the only time people are really interested in science, is in social media discussions, isn't it? In social media discussions, science seems to be such a winning argument. I mean, if you drop a scientific fact, then you basically win the discussion, right? Which is basically why we have discussions anyways, I guess. But as a scientist, that has always bad for me, okay? Because if there's one thing I learned in science, is that David Freeman was right when he said, the more we know, the less we know, and the less we know, the more we think we know. So quite honestly, what people want to know is when can I go to the doctor get some of it? Simply, and it's fair. And I think there's only one way to describe the current situation we find ourselves in as it relates to stem cells. And that is to say, we have reached a critical point in the history of stem cells. A point that can only be described as this. What you see is a massive number of different stem cell treatments out there. And really, the only thing between them and us are regulatory agencies, such as the FDA and the US. But the number of stem cell treatments out there are getting so overwhelming, the sum are just falling through the cracks. And the question then is, how did we get here? And what does that mean to you? So the first thing we have to understand is that stem cells really exist within a relative large spectrum. Okay, it starts with the embryonic stem cells, goes through your postnatal adult stem cells, all the way to adult cells that we can now genetically reprogram to become embryonic like stem cells. We call those induced pre-reportant stem cells or IPS cells. Now we knew from the beginning that embryonic stem cells offer perhaps the greatest differentiation potential, which is by the way what defines a stem cell. It's a cell that can replicate and giving the right cue, it can differentiate you to something else, hopefully something useful. But we've always known that great differentiation potential also means the greatest risk. And it's a very simple concept to grasp, right? We tell our kids, I tell my kids, they can be anything they want when they grow up, right? Don't you? Except the chances of my son become a professional basketball player are probably really slim, right? But I don't tell them that. But we also know that there are very specific conditions in environmental factors that have to be present just for a kid to become a functional contributing member of our society. And more often that we like to admit those conditions are not met, they're not in place, and a lot of the kids end up going astray. Unfortunately, when it comes to embryonic stem cells and IPS cells, going astray really means turning each cancer. And that's the last thing we wanted. Now as I speak and I say in an upset a lot of scientists by oversimplifying something very complex, there are many scientists working precisely on deciphering those conditions. And in the future it's quite possible that the choice between using embryonic stem cell and IPS cell will come down to a moral choice. And with that being said, I have to tell you that both embryonic stem cells and IPS cells represent a very small fraction of all the stem cells out there. What makes the bulk of them are really adult stem cells. And going in, we knew that adult stem cells have a limited differentiation capacity. After all, they already decided to be something or on the road to become something. But then 10 years ago something happened that can only be described as a paradigm shift. These cells are better, a subset of these cells, we call them mesenchymal stem cells or MSCs for short, were able to treat and improve a lot of experimental models of disease from heart attack, type 1 diabetes, neurological diseases without ever needing to differentiate into anything. And after 10 years of research I can tell you that the way they accomplish such features is by simply going at it, is by simply doing everything a cell can possibly do. In fact that's why we still call them adult stem cells because you do find them at various ages. But can you imagine that there were teenagers stem cells? I mean, first of all they wouldn't like to go there because they would be boring, right? But they would get there and they wouldn't do anything. It just being tied up that the whole disease would just treat itself because they were there. I mean nothing would get them, right? But as responsible adult stem cells, they go to work. And they employ a plasera of different molecular mechanisms, things like genetic transfer, transfer of mitochondria, secretion of venting flammatory proteins, secretion of gold factors that combine we modulate key systems in our body. I'm talking about your vascular system, your immune system. And there may be other stem cells that have in your body. And they modulate them towards healing as simple as that. And I challenge you to think about any disease or condition. And I can guarantee you it would benefit from either one, if not all of these interactions. And that's precisely what's causing the stem cell revolution we see today. But that's not all. Something else happened. It turns out we discovered we can find these cells virtually in every organ in your body, including your adipose tissue, your fat tissue. So what I'm telling you is that you could have a stem cell treatment at the same time you have liposcopy. And in a country like the US where the number of liposcopyers or liposperate procedures reaches almost 300,000 cases a year, you combine it with a relatively simple method to isolate those stem cells. Then you create the perfect environment for the resurgence of doctor's staining. And I'm not saying doctor's staining had embedding tensions in his heart. In fact, I think we should have followed this whole snake oil thing. But the fact is that in the US, particularly, the FDA has not yet approved a single stem cell treatment apart from stem cell per bone restoration in some cancer cases. All the other stem cell treatments are not yet approved by the FDA. And the FDA is really strict. Actually, it's the strictest regulatory agencies in the world. But I do tensioning towards safety as well. Because that's what we're really talking about. And there are hundreds of clinical trials which are really dead. That trials, studies, assessing safety in efficacy in a very limited number of patients. And I think it's quite simple to understand why someone would be concerned about those cells. Cells are not drugs. I could manufacture a drug here, send out to Brazil, and they would manufacture the exact same drug. But I cannot guarantee that my stem cell, in your stem cells, will act and behave the same. And I think that everything else needs to be a little bit different. And what's worse, if I can get your stem cells, I start growing them and I give some to my colleague down the hall a few weeks later, and when we come back and compare them, they might be different. And the last thing is, we know they do a lot of things. But we don't know quite how to control them. And once really rare, Dr. Stainless is popping up everywhere in the country. And we then come to horror stories. And I'll share two of them with you today. First one is a middle-aged woman, a woman who saw an advertisement for facelift in stem cells. Facelift in stem cells. Now, I know a few scientists who work with stem cells, none of which work with facelift. But this physician, in particular, decided it was a good idea to inject stem cells in this patient's face around her eyes. And a few weeks later, she woke up, and every time she blinked, she heard a click. And you can think that's cool for a second and two, start freaking out. And it turns out that stem cells in her face decided to turn it to bone. So she needed to have them surgically removed. And granted, this happened 10, more than 10 years ago. The second story is really recent. It happened this year. There were three older patients who suffered from a degenerative disease of the eye, and they also saw an advertisement for stem cells. And the physician, in that case, decided, well, let's go step further and inject these cells inside her eyes, directly into her eyes. And a few weeks later, I'll win blind. And what's worse about this case is that the physician, he had the trouble to go to the FDA and start a clinical trial. So he could falsely advertise that his procedures were somehow legit. And so we have really come to a point in history in which the most reliable source of information when it comes to stem cells are really scientists. And that's very scary. I'll tell you that. There was a survey done in Florida in which they asked people, how do you first hear about scientific discoveries? And out of 13 different possibilities, scientists ranked number nine, which means more people learn about scientific discoveries by the way done by scientists. Through comic books, sitcoms, and movies. That's how people hear about scientific discoveries. And I think that's largely fall of the scientists ourselves. We are largely a focus. You know, being from Brazil, I think the biggest difference between Americans and Brazilians are Americans that should take themselves a little bit to serious. And I think it's because you guys don't have enough problems. You don't. Right? In Brazil, there's so many issues, so many problems. We can't afford to make ourselves another one. We wouldn't get out of bed. But here, people tend to think themselves a little. I'm not saying we shouldn't take what you do seriously, because I think we do. And we must. But we shouldn't take ourselves to seriously. And scientists fall from the same disgrace. And what we really need, I think, is scientists, as scientists, we need to get out of our heads a little bit and reach out and inform people about STEM cells. Because quite frankly, a simple message could have prevented those disasters. And a simple message would most likely prevent future ones. Because STEM cells are coming. We just have to make sure the good ones make it. Thank you. | ↗ |
| 76 | Dr Adeel Khan & Eterna Health | Reprogramming Cells to Reverse Aging: The Future of Longevity #shorts | 1455 | 53 | 2 | 59.0 | negative | 0:59 | So what's else possible today? Um cutting edge um advancement and technologies we can do. Uh I think we mentioned most of it. Did we forget something else? Well, there's a lot but there's I I think one of the most exciting parts is cellular reprogramming which is like we were talking about as a software engineer you can appreciate this. Imagine you can program your cells to do what you want them to do. So for example, you can make old cells young again and those are those are called the Yamanaka factors. So my gray hair turned out to be yeah those are those are things that are being worked on by a few different companies right now and so that's cellular reprogramming I think is going to be really the future of let's say a lot of chronic diseases and aging as well and so that that's where I see the most potential right now and you combining that cellular reprogramming technology with different gene therapies is probably where what's going to lead us to what we call longevity escape velocity where it's just like you can live a very long time and healthy uh for that period of time too. | ↗ |
| 77 | Iman Bar M.D. | Reverse aging by 15 years. Visit us at Newport Beach, California 👀 | 29 | 3 | | 58.8 | | 1:23 | What if one injection could reverse the case of aging and eliminate chronic pain? I know that sounds crazy, but regenerative medicine is changing what we understand about healing. And now research showing that stem cells can rejuvenate damaged tissues, speed up recovery, strengthen immune function. And in some cases, improve biologic age even up to 15 years. In order to achieve this results, there is the procedure on how the cells are prepared and how the patient is optimized and how therapy is delivered. The way we do it here in the United States, in Orange County, before ever extracting any stem cells from your body, your body gets prepared. First, we do detailed labs, IV therapies, ozone, hyperbaric, a lot of treatments to clean up your internal environment because we need to extract your own stem cells. One at a time for treatment, we use shockwave therapy, hyperbaric, laser therapies to activate the tissues, and we use ultrasounds to guide the placement if it's in a joint or in the back precisely. This is one of the best regenerative protocols designed to eliminate chronic pain, reverse aging, save some people from having to get a surgery altogether. It's the ultimate therapy of the century to reverse aging, improve your immune system, reverse breakdown, and regenerate you to a younger you. | ↗ |
| 78 | TEDx Talks | The Potential of Regenerative Medicine | Stefano Sinicropi | TEDxMinne... | 822 | 25 | 11 | 58.7 | positive | 17:59 | No transcript | ↗ |
| 79 | Graduate School of Biomedical Sciences at UT Health San Antonio | What is Translational Science? | 13974 | 112 | 2 | 58.5 | positive | 7:30 | Wow, that's going to be a tough act to follow. Hi everybody, my name is Essence Chaudhary. Camera man, I'm sorry, but you're going to have to follow me around. He's going to hate me. First of all, I want to thank Teresa, Charlotte, Nicole, and Laquisha for helping put this together. Thank you very much. We need this. I'm a student in the Translational Science PhD program. So when I told somebody about my degree, what I'm seeking it in, this person asked me, oh, so what language are you studying? And I said, no, sorry, I'm not translating Swahili in English. I'm studying a multidisciplinary science. So Translational Science was started here at the Health Science Center about five years ago. We have a pretty small class. And the purpose of Translational Science is basically a little bit of what we're doing here today. It's the interprofessional interaction between scientists, physicians, dentists, physical therapists to try to find innovative discoveries to some of the most chronic and some of the most critical care needs in terms of disease that we have today. So Translational Science looks to try to speed the discoveries in the clinic into discoveries of the bench side to treatment in the clinic and then assess which of those treatments in the clinic are most effective, cost-effective, and to try to make best medical practice guidelines based on that. So in a nutshell, that's basically what we do. So as scientists, we're kind of experts in our field, but we are also liaisons into the other sciences. So we try to hope people up, so to speak. So it's non-traditional, much like me. I'm going to give you a little bit of a background. I graduated Texas Lutheran in 1999. That's a long time ago. I came to Utahscar to do research. I've done research here before I was a student for about 10 years almost. And then I was also in the guard. I was a chief warn officer and I was a chemical, biological, radiological, nuclear tech. So as a, yeah, that's a mouthful, say that three times fast. So as a warn officer, I was an expert within my field, but then at the same time I was a liaison between the officers and being listed. So that was a perfect fit for my translational science program. It was very non-traditional. And so I continued my research and I originally thought that I wanted to go to medical school, be an emergency room physician, go with a special forces around the world, but then I met her. And she said she probably couldn't be with somebody who's deployed all the time. So I had a tough decision to make. I chose her, obviously, right? So then I thought to myself, okay, if not a physician, what do I want to do? I want to have patient contact. I want to have interaction with patients. I want to work in a multidisciplinary field where I can talk with people from different disciplines. Try to work on something innovative. And so fortunately, the translational science program was started here at the Health Science Center. So I applied. I got accepted and never in my life have I felt so supported and welcomed as I have in the graduate school and the translational science program. And here at Utuska. And so on a daily basis, I get or interact with people who have a drive and a vision that's greater than mine or at least equal to mine. And that's inspiring. All of you have a vision. All of you have a goal that one day you want to put to work. You're going to be playing a critical role in healthcare. And so we all have different areas of our experts in. So if we learn to communicate in an interdisciplinary way, come to the table, talk, become friends, we can get a lot done for the critical care needs that we have in healthcare. So real fast, I've been fortunate to kind of find my life's journey, I think. I am involved in some science communication things because science belongs to us all. The problem is that a lot of scientists don't necessarily communicate science as effectively as one would hope. And that's the fault of some scientists. So to be able to do that, you have to be able to speak clearly, you have to be able to communicate what you're doing in a way that's accessible to everybody. And so fortunately I was involved in an event called Science Fiesta that Travis Block over there helped to organize along with Miloš, a Meringuevic. And so that was a great way of getting involved in science communication portion of it. Luckily I'm also working on trying to set up something that's related to crowdfunding for a lot of young scientists, try to get Biotech built in San Antonio. We have a great Biotech city. A lot of people don't know that. And so to try to get the word out, to show them how wonderful the health science center is as a part of the Biotech industry in San Antonio is critical. Another interest of mine is innovation through public-private partnerships. So fortunately there has been, I have a friend who's a CEO of a startup company here. He's bringing his technology into the health science center. And it's a technology that helps scientists manage big data. In the world of genomics, proteomics, metabolomics, a lot of big omics, a lot of big words. But basically we have a lot of information we don't know what to do with. So he has software that can help scientists manage that better. I also work in a technology consulting group, so that works with the office of tech commercialization. Excuse me, tech commercialization. And so we try to help bring some of the newest discoveries at the health science center to clinics and to try to bring them to consumers. So they can find that treatment quickly. But I think the most important thing is that we have to work effectively as a team to be able to tackle these problems that I was talking about. It's our responsibility as contributors to healthcare. Each one of us, whether you're a physical therapist, a dentist, a nurse, a physician. We all have a responsibility not only to patients, but to ourselves as professionals across disciplines to build the kind of relationships that we need to carry this forward and to find treatments and cures for cancer. And diabetes and heart disease and all the kind of maladies that are out there. So this is only one of the reasons that we need to reach out across schools, across disciplines, and to try to understand each other's life journey. And I think that this is a great form to do that. Thank you. | ↗ |
| 80 | VSI® | Spine Solutions | Does stem cell therapy really work? | 9906 | 107 | 20 | 58.4 | neutral | 0:48 | So, I've seen a lot of trending videos on Tik Tok and Instagram where doctors are saying that regenerative medicine and stem cell therapy doesn't work. I can tell you that's simply not true. I have taken care of hundreds of patients and I've had them reclaim their lives, improve their mobility, improve their pain by the use of stem cell therapy and regenerative medicine. This is a very safe treatment that some people are claiming can cause cancer, but it's not true. We use the patient's own body to start healing themselves. If you think that stem cell therapy may be beneficial or we were wondering, send me a DM, call the office. Be happy to kind of discuss this with you. Please don't let misinformation stop you from getting the right answers. | ↗ |
| 81 | Dr Aiden Core | Senior Health | "THIS Root Vegetable Doubles Stem Cells & REVERSES Aging" – Eat This E... | 9695 | 544 | 20 | 58.4 | neutral | 24:31 | No transcript | ↗ |
| 82 | Rozenhart Family Chiropractic | What is Regenerative Medicine? | 860 | 19 | 2 | 58.4 | positive | 0:43 | What is regenerative medicine? That's a great question. I have my pal here, Mr. Lizard, to tell you all about what that actually means. So whether you know they're not lizards, have the capacity that if they lose a tail, they are able to regenerate or regrow a tail. Most humans do not have that capacity, but with some changes in modern regenerative medicine, we can actually help cells and tissues regrow. Using some processes like PRP, PRF, even stem cell is part of regenerative medicine. Helps your body recuperate, restore, and actually grow new healthy tissue. If you have any questions about that, please comment below. We're happy to answer. | ↗ |
| 83 | Stem Cell Institute | Joe Rogan and Russell Crowe Discuss the Benefits of Stem Cell Therapy | 41184 | 575 | | 58.3 | | 3:54 | No avoiding, but what I do want to get in the get I guarantee stem cells will help that I've had tremendous success with stem cells In shoulder joint. Yeah, yeah I was told by a doctor that I was gonna have to have shoulder surgery He said well he did all of these exercises we pushed down on it and we did an MRI He's like it's so torn he goes you could try to rebuild it. No, it was a little bit of labor I'm but it was I had a full-length rotator cuff tear. Okay, and he's like it's gonna have to be repaired So it's trice stem cells and he was doing them for the UFC and you know This was they could do some pretty potent stuff This is before some of the new regulations have come into place that they're constantly trying to regulate the stuff because it's very effective Well, I went in he shot me up. I took it easy on it. I did rehab I started doing all these band. I used these cross-over symmetry bands and I started doing all these exercise to build my shoulders back up And then it started feeling pretty good and I started working out again and just being real careful As soon as I feel pain I'm gonna stop I went back to him in six months. He got an MRI But he said it was the most extraordinary thing he's ever seen He said the tear is gone. He said I've never seen this before because I've never seen this all my years being orthopedic surgeon I've never seen a tear and there's a new study that came out that's showing that they're able to regenerate cartilage tissue And this is very very promising so with when they're able to do this kind of stuff now If you could just hang in there here you go Jamie If you could just hang in there for just a year or so I guarantee you they're gonna be implementing this stuff on people I've got no cartilage in my big toes no cartilage left Because all the sports I used to do a lateral My toe yeah, and but also you know Sometimes the shit goes wrong in a stunt and you got a stop or you die Right so this is it insulin like growth factor one in Articular cartilage repair for osteosaritis treatment so That they're able to do this Signaling pathway that's been implicated in art articular cartilage repair IGF1 is a member of the family of growth factors structurally closely related to pro insulin Cabromote I don't know what that word is cron cron dice cron dro site prolification Enhanced matrix production and inhibit Catabolism more over we discussed the potential role of IGF1 and OA treatment of note We summarize the recent progress on IGF delivery systems Optimization of IGF delivery systems can facilitate treatment application in cartilage repair and improve OA treatment efficacy So there's this and there's another one that's in Australia where they're they're using it on cheap right now And they're able to regrow cartilage on cheap and they're about to begin human trials on that as well here Human discovery and animal models could sue into new human therapies So this is this is the next stage right because right now there's nothing they can do about cartilage What stem cells have been really effective at is soft tissue injuries Tending repair things along those lines and a lot of neurological disorders that people have especially IV versions They've done a lot with Dr. Neil Reardon and Panama's had some great results with that and great results I Mel Gibson came in and talked about his Experiences with that and his father his father was in a wheelchair when he was 80 Ten years later at 90 was walking around and this is after stem cell Okay, it's as they can do some pretty extraordinary stuff especially and growing dist issue on people that have Disgeneration issues It's just we're real close we're real close to being able to regenerate all kinds of stuff So just got to hang in there yeah hang in there But I guarantee you what the stem cells can do is help heal what can heal in that area reduce inflammation Give you more range of motion and give you a much more pain free experience because | ↗ |
| 84 | Mark Hyman, MD | What Is Regenerative Medicine? | 3443 | 105 | 5 | 57.8 | negative | 1:34 | What is regenerative medicine? I mean we talk about functional medicine which is a systems approach to addressing chronic illness. The looks of the body as an integrated dynamic system and that health is really about creating balance in these systems. It's not really about treating disease per se. And you have now kind of combined that with an approach that's called regenerative medicine, which I see is really more or less the same thing, but more dealing with some of our structural biomechanical issues and pain. So talk about what is regenerative medicine? Okay, so that's a good one. Like I've never thought of defining it like that, but I would define it exactly how you said. It's a systems approach to musculoskeletal medicine. And so then we're looking either from outside all the way in or from inside all the way out. So we're looking at from the level of the bone marrow to the joint to the joint capsule, the menuscus, the fascia that affects how kinetic force moves through the body, nerves, ligaments, intendons, and sort of looking to see, are there any problems at any of those levels? Is there a systemic problem? And then trying to figure out strategically what our targets are in terms of where problems are. And then having a thoughtful approach to addressing any one of those problems with a product that has a potential to hopefully heal those tissues, whether that be a tendon or a nerve or a joint. | ↗ |
| 85 | Keck School of Medicine of USC | Stem Cell Research and Regenerative Medicine at USC | 17474 | 166 | 17 | 57.7 | positive | 2:40 | There are different types of stem cells in our bodies. The stem cells that are in testing, the stem cells in our skin are kidney. All of those stem cells have the capability of generating any cell types within an organ. We can repair our skin when we get a wound, our liver is regenerate. However, a lot of our organs regenerate very poorly. We are everyday identifying new stem cell populations that allow us to think about replacing tissues in the body. What we're trying to do is understand the fundamental basis of different diseases. How can we regenerate function where function is missing? Hearing loss and balance disorders are really major problems. The sensory hair cells of the inner ear are extremely fragile and they die for lots of different reasons and we want to know why. We are looking for ways of preserving these cells or regenerating these cells after the loss of the sensory hair cells. We can make stem cells that are much to the patient immunotype. Neurodegenerative diseases are a huge problem in the aging patient population. How can we figure ways out that we can generate the cell types that are degenerating in the patient and put those back and try and repair that disease? One great advantage is zebrafish is that they share many of the organs that we do, skeleton, heart, liver. In addition, zebrafish and us have 95% of our genes in common. So we can make the same mutation in zebrafish and get the same sort of organ defects that you can in human birth defects. What's happening with those cell types within the patient? Why do they degenerate? Can we figure ways out that we can stop that happening? This is the most interesting question you could possibly want to work on. One reason I think that USC is such a great place for research is that there's such a breadth and diversity of developmental biology and stem cell research here. Collaboration allows us to bring the most modern developments in stem cell biology to bear on the problem of regeneration. Each of us is an individual. We are all different. We all may seem to have the same disease, but in fact it's maybe all a little bit different because of our different genetic makeup. Regenerative medicine is going to be very important in future years. Manipulating cell populations within the body will allow us to cure disease and that potential is seemingly unlimited. This is going to have the greatest impact in the future of medicine. | ↗ |
| 86 | HealthTree Foundation for Multiple Myeloma | What is translational research? | 5515 | 64 | 1 | 57.6 | positive | 2:21 | What is translational research? So translational research is the middle ground between basic science research, which is very basic fundamental biological research and clinical research, which is clinical trials when we test new therapies with patients. So translational research is a fairly broad field. It covers any sort of disease biology associated research. And that can be many things. It can be a laboratory model that you do in a dish, but it has many of the elements of the human disease. So in myeloma, you hear a lot about bone marrow stromal co-culture models. That sounds really complicated. But what it means is in a dish, we're trying to recreate the bone marrow microenvironment of myeloma. There's bone marrow cells such as stromal cells and stem cells and then myeloma cells so that you have kind of a recreation of the bone marrow microenvironment. So that's one example. A second example is an animal model. So you hear a lot about zina graft models or engineered animal models of myeloma. Sometimes you can take myeloma cells out of a patient and transplant them into a mouse and then treat those mice with drugs to see if they work in a living system. So that's another example of translational research. Or you can take cells out of a patient, the myeloma cells or other types of cells out of a patient and analyze them to see if you can identify genetic mutations, for example. So anything that touches on the actual disease, whether it's a laboratory model or experiments that you do with actual tumor cells from patients or other material from patients such as bone marrow, immune cells and so forth. These are all examples of translational research. Thanks for watching. By creating a health tree account, you can get exclusive access to the latest health tree university content, track your course progress, take quizzes and bookmark lessons, visit the links in the description below to get started. | ↗ |
| 87 | Doctor Leana⚕️ | SENIORS: "THIS Coffee Trick REACTIVATES Stem Cells & STARVES Cancer" –... | 225931 | 8599 | 277 | 57.4 | positive | 29:40 | No transcript | ↗ |
| 88 | VSI® | Spine Solutions | Is Stem Cell Therapy FDA Approved? Dr. Bharara Explains. | 53534 | 846 | 48 | 57.4 | negative | 0:41 | There's a lot of information and misinformation out there regarding stem cell therapy. One of the questions that I get very frequently is, are the stem cell procedures that you perform FDA approved? Now, this is a confusing question, but simply put, the procedures that we perform are FDA exempt. The FDA does not regulate the procedures that we perform because we use the patient's own bone marrow and blood to perform the actual procedure. Now, if these procedures were performed by using somebody else's tissue like their blood or their bone marrow, then these would fall under the FDA regulation. | ↗ |
| 89 | Doctor Rich | Live Stem Cell Injection Therapy #drrich #doctorrich #stemcells #stemc... | 6342 | 101 | 3 | 57.3 | positive | 1:01 | Hey guys, it's Dr. Rich. I'm sure you've heard of stem cell therapy. So what are stem cells? How are they acquired? Well, in many cases, they're harvested from the recipient's own bone marrow. So check out this video where I get a live bone marrow harvest. Coming to you live from Seattle, she is a board certified anesthesiologist, her Lucie Hostetter. Thanks so much. Let's get this done. Let's do it. Okay, I'm going to put a little plastic drain on it. Okay, so here comes the broken burns. This is just the locals and the light of cams. Might... That's one of them. Okay. Yeah. | ↗ |
| 90 | Investigate Explore Discover | Unraveling Cellular Reprogramming: Insights into Lineage Conversion wi... | 272 | 12 | | 57.3 | | 0:57 | Direct lineage conversion, a process that transforms cell identity through transcription factor over expression relies on the reconfiguration of gene regulatory networks, GRNs. To shed light on this complex process, scientists have combined computational analysis and experimental lineage tracing. Using cell oracle, a computational method that infers GRNs from single cell transcriptome and epigenome data, they simulated gene expression changes in response to transcription factor perturbation. Linking early network states to reprogramming outcomes in fibroblasts, to induced endoderm progenitor conversion, they identified distinct network configurations associated with successful and failed fate conversion. Through in-silico simulations, they uncovered the involvement of new factors, including the AP1 subunit boss and the hippo signaling effector YAP1, in driving successful cell identity conversions. This study showcases the power of cell oracle in inferring and interpreting cell specific GRN configurations, providing valuable mechanistic insights into lineage reprogramming. | ↗ |
| 91 | Rory Anderson | The Future of Longevity: Inside Biohackers World 2026 (Exosomes, Pepti... | 15 | 2 | 1 | 57.1 | positive | 1:05:31 | No transcript | ↗ |
| 92 | Dr. Daniel Yadegar | MUSE cells EXPLAINED | 15 | 1 | | 57.1 | | 1:24 | I'm saying a lot of info circulating on Insta on new cells. Can you explain what they are and do? So this is a really hot topic. It's still in its early phases and investigational. And we're starting to understand better. So certain kind of stem cell, a mesenchymal stem cell, these cells, when they're injected into your body, have like an ability to know where damage and inflammation and recoveries needed. And they go to that particular organ. It could be your heart, your liver, et cetera, and actually help with regeneration. I've heard with stem cells like this that they can also regenerate harmful cells. Is that the case with new cells? That's a great question. We always worry about the possibility that stem cells can actually encourage like tumors or cancer. Because if they're giving your body an adaptive advantage, it can possibly give a cancer cell an adaptive advantage. The reason new cells are exciting is that the preliminary data shows that it's mostly non-tumorogenic, meaning that it doesn't seem to be encouraging cancer and still offers you the benefits of regeneration. The implications for this could be massive. It could be people with liver cirrhosis, people with heart troubles, people with chronic lung issues, the new cells, because they can differentiate into any kind of stem cell or actual any kind of cell can really help you with all sorts of disease states. Really exciting science. | ↗ |
| 93 | NBC News | Warning Over Controversial Stem Cell Clinics And Unapproved Treatments... | 117307 | 581 | 197 | 57.0 | negative | 3:32 | We're back now with the controversy over stem cell clinics. Earlier this week, the president's new pick to head the FDA was grilled by lawmakers about government regulation of rogue clinics. NBC Medical correspondent Dr. John Torres is here with more. So why the concern? So Kate, it's the Wild West of Medicine. Stem cell clinics targeting vulnerable patients with misleading ads that claim to treat everything from joint pain to diseases that have no cure. There are now over a thousand of these stem cell clinics across the US, some using unregulated stem cell treatments that may be illegal and in some cases even harmful. They said that there was no chance of anything going wrong because it was coming from my own body. 79 year old Doris Tyler tried stem cells after reading a promotional book by the founders of cell surgical network. They claim stem cells could treat macular degeneration, an eye condition with no cure. Cell surgical network referred Doris to an affiliate clinic in Georgia, where doctors took stem cells from fat and her stomach and injected them into her eyes. Three months later, she was blind. An ophthalmologist who examined Doris after the treatment says her vision loss is more likely than not the result of the stem cell procedures. No, that total darkness was all I was only ever going to say again. Doris is now suing the Georgia clinic and cell surgical network. The Georgia clinic declined a comment and in a statement to NBC News, cell surgical network says cell surgical network is a teaching research company and owns no clinics. We cannot discuss any details since it is being litigated. Our research group was involved in 12 macular degeneration cases over a four-year period and 10 reported improvement in their vision. Dr. John, are these treatments approved by the FDA? Kate, most of them are not. In fact, these centers are popping up so fast the FDA is having a hard time monitoring them all. We visited one stem cell clinic, which is using unregulated treatments. Okay, you may feel a little needle. So this is the bone marrow you took from the patient? Yes. And after processing, these are the stem cells you can put back into the patient in the area that they need treatment. Exactly. Dr. Benjamin Bieber charges between four and eight thousand dollars per treatment for rotator cuff tears, hair restoration, even erectile dysfunction. The FDA says that stem cell therapies are only approved for blood and immune disorders, but today you treated somebody for hip condition. I'm not involved with the politics. I just want to make my patients better. And I know over the last seven to eight years using stem cell therapy has made a big difference in people's lives. But the FDA warns more research is needed. Dr. Peter Marx evaluates stem cell treatments for the FDA. Orthopedic conditions to kidney disorders, to neurologic, you know, brain problems. There's not evidence that we have that they're safe and effective yet. So if the FDA is saying there's no evidence that they're safe and effective, what are they doing about it? Okay, the FDA told NBC News they plan to crack down on unapproved clinics next year. But with the new FDA commissioner taking over, we'll have to wait and see. | ↗ |
| 94 | Cell Press | What to Expect if You Participate in iPSC Research | 2262 | 21 | 2 | 56.5 | positive | 3:31 | Recently there have been major technological breakthroughs that allow us to take an adult cell such as a skin or hair cell, turn it back into a stem cell and then from that stem cell differentiate it into another type of cell such as heart, eye or brain cells. These are called induced pluripotent stem cells. Essentially this means that we can study the cells in your brain or eye without needing to actually take a sample from your brain or eye. The hope of this research is that if we can understand what is happening in these cells, then we may be able to come up with better ways to treat disease. The biggest downside from participating is that you will be left with a small scar about the size of a large freckle. Another major downside is that you will not directly benefit from this work. It is likely to be the next generation who have the most to gain from your contribution. Before agreeing to participate it is important to understand a few things about your sample. Firstly, the stem cells that we will make are different to other cells in your body. They can survive indefinitely, that is they can continue to divide and grow where other cells in your body, such as the original skin cell, would have stopped. Also, these stem cells can, under the right conditions, be turned into any other type of cell in your body. It is important to realize that your sample will not be injected into any other person and that the stem cells made from your sample will not be used for research involving reproductive cloning, that is to make another human being by creating an artificial embryo. Sometimes to test things, such as confirmed that the stem cells we have made are actually stem cells, we may inject these into animals such as rats or mice. As new breakthroughs occur, it is also possible that your sample could be used in an experiment that is not envisaged at the moment. Any new research would require ethics approval. Your sample will be used to help advance the development of new treatments and tests for disease. This research could lead to cell replacement therapy, where disease, tissue or cells are replaced with new ones. This work could involve pharmaceutical companies, though they would also need appropriate ethics and regulatory approval. After participating, you can withdraw from this project without any consequence on your medical care. If you withdraw, all of your samples can be destroyed. However, we can generally only stop future research, not destroy work already completed. Finally, there are different levels of participation possible. Occasionally, we are approached by other researchers who are doing similar work. Would you be happy if we shared your sample with them? They would need ethics approval for this research and they would not know any of your personal details. After today, your sample will just have a number on it and it will only be the lead researchers who can unlock this code and link your sample directly back to you. Secondly, one of the ways that your sample can add value after its collection is to use it for additional studies. Would you be happy if your samples are used for additional research? For example, if you have participated in eye research as well as a brain study, then your cells could be used for both eye and brain disease modeling. There are specific tick boxes on your consent form where you need to indicate if you are happy for this to occur. Please take your time to read through the information sheet and consent form and please feel free to ask any questions. | ↗ |
| 95 | Kevin Logan, MD | Day in the Life of a Regenerative Medicine Doctor | 2392 | 7 | 1 | 56.4 | positive | 5:34 | Good morning. It's bright and early. We're getting ready to get started. We have eight procedures today. We're going to do regenerative medicine. Over the last 30 years, I've been practicing functional medicine, but my practice has changed and evolved over the last seven to eight years with the addition of regenerative therapies. Once a week, I have days like today where I focus just on regenerative therapy and I've honed my skills by attending multiple conferences and studying with some of the greatest minds to learn new techniques for injections, for treating nerves, and all this off-tissue that surround a joint to allow that person to heal and get back to full recovery and activity. Today is a procedure day. We'll be seeing eight patients today. We'll be treating a variety of conditions from chronic rotator cuff injury, knee injuries, and osteoarthritis, and a variety of other musculoskeletal conditions. It's a busy day today, so I better get going. I've got a couple minutes to get organized and we'll see you in there. This is a very satisfying part of my work because I see people get back to their game whether it's golf, tennis, or even just walking their dog. This process begins by extracting one's blood and then spinning it in a special centrifuge to release the growth factors from these cells called platelets, which actually facilitate the healing of the body. They also facilitate the mobilization of stem cells from surrounding tissues to help with the regenerative capacity of the body. It's powerful because we're using all their own healing potential that comes right out of their veins and then we process this very quickly, give it back to the body. The body knows exactly what to do, which is repair and heal and regenerate, which is what our bodies were intended to do to begin with. This is just another very effective tool to deliver precise growth factors and nutrients that are going to help that tissue recover. This is the ligament here. You have a superficial structure and then you have a deeper structure. It actually attaches to the medial meniscus. That's your medial meniscus right there. It's not completely attached right there, and that's going to be one of our targets. They get back on their game, they win matches and they come back satisfied and that makes my day. I just got done with that procedure. It went really well and I expect to see him back in about four to six weeks and we're going to start working on his shoulder next. So now I'm going to go get some lunch. Lunch today, I like to eat local, so this is a sirloin tippros from Shocked Farm, a local sourdough. We've got raw grass-fed butter, which is rich in vitamin A. You see the yellow color and then fresher regular out of the garden. Part of my prescription for my patients is lifestyle medicine. This includes movement, nutrition and high quality sleep. Movement after a meal is a very easy way to actually lower your blood sugar. The research shows you can lower your blood sugar by 10 to 20 percent with just a short 15-minute walk after you eat. Today I had extra time, so I actually got in around a Pilates to lower my blood sugar levels and get my blood circulating, so I'll have plenty of energy for the rest of the afternoon. On to the afternoon appointments. My next patient is a person who is a D1 wrestler and he's had some shoulder injuries. This is his third treatment. He's getting good results. He's getting back on the golf course and swinging well and he's getting his strength back, so super excited to see how he's doing today. That just helps to help that joint heal. I mean you've made great progress. This is number three. So this is a fairly straightforward procedure. With a shoulder, as with all joints, I do a very comprehensive treatment of the joint. So that includes muscle and tendon connections to the bone, ligaments which connect bone to bone, as well as the nerves that innervate the structure, whether it's shoulder or knee or whatever it is. We always want to make sure we're treating those nerves because those nerves are feeding the joints which is increasing blood flow and it's going to facilitate healing as well as reduction of pain. Normally Monday through Friday, I'm seeing patients and I'm applying the functional medicine skills and internal medicine skills that I've acquired over the last 30 years to do a deep dive into what is causing their particular illness and helping them recover from that. This is actually a very different day because we see people recover and get back to their daily activities much quicker than they would if they had surgery or steroid injections. Knees and shoulders are the most common joints that are treated because those are what people present with. Hips are also another common finding and then we can treat a variety of other joints including elbows, ankles, etc. Hi, thanks for watching the video today. When I have time, I love to make these videos because I love to educate about health and wellness. If you enjoyed this video, please make sure and subscribe and maybe check out this next video. YouTube thinks you're going to like this one. If you have any questions you'd like me or my team to answer, please leave them in the comment section below. See you in the next one. | ↗ |
| 96 | Doctor Becker | SENIORS: Add THIS to Your Morning Water — Cancer Starves, Stem Cells A... | 67540 | 2486 | 96 | 56.3 | neutral | 39:07 | No transcript | ↗ |
| 97 | worldstemcell | Cellular Reprogramming Animation | 49540 | 370 | | 56.2 | | 2:47 | in order to create induced plur potent stem cells a large population of reprogrammable somatic cells is required many sematic cells have been successfully reprogrammed however fiberblast cells are commonly utilized because they can be easily extracted from a patient using a safe and non-invasive skin biopsy and are easy to culture in a lab fiberblast cells are somatic cells that produce connective tissue morphologically the cells appear flat and they secrete collagen and elastic fibers that make up The extracellular Matrix every cell type in an organism apart from gyes and undifferentiated stem cells are somatic cells each somatic cell has a unique structure and function due to a distinct combination of genes that the cell actively transcribes and translates into functional proteins the difference in gene expression between different somatic cells is largely due to the structural organization of the chromosomes in each cell chromosomes can exist in two forms the DNA can either be tightly wound around histone proteins to yield heterochromatin or the DNA can be Loosely Unwound to form UK chromatin this Loosely Unwound DNA permits The Binding of transcription factors and other transcriptional Machinery such as RNA polymerase to the Gene's promoter region once the transcriptional Machinery has bound Gene transcription begins and a molecule known as messenger RNA is made when the DNA exists in a tightly wound configuration the DNA is not exposed to the transcription machinery and transcription does not occur in this manner the cell can regulate the genes it does and does not express in fact out of the 20 to 25,000 genes of the human genome a somatic cell will only express a small fraction of the genes at any given time and the rest of the genes are considered transcriptionally silent this is the case for the reprogramming factors OCT 4 sock 2 klf4 and cmyc in the fiber blasts because these genes are not actively expressed scientists must induce the expression of these genes artificially using transgenic strategies there are a number of methods available for artificially overexpressing genes in a Cell the yena group utilized retroviral vectors as the method to deliver the trans genes encoded for the four reprogramming factors oct4 Sox 2 klf4 and cmyc the retroviral vectors deliver the four trans genes into the cells the trans genes are then integrated into the host's genome thereby permitting its long-term gene expression amazingly when the four trans genes are coexpressed in the same somatic cell the differentiated cell is reprogrammed into a plur poent like state | ↗ |
| 98 | Dr Aiden Core | Senior Health | Chew This Before Bed – Watch Your Stem Cells Rebuild While You Sleep | 1145 | 66 | 3 | 56.2 | positive | 28:10 | No transcript | ↗ |
| 99 | Interventional Orthopedics of Washington | Is Stem Cell Therapy For Everyone? | 27787 | 453 | 13 | 55.8 | neutral | 0:45 | The biggest breakthroughs are in the combinations or the special recipes that give you the type of therapy that you need for your condition. So it's really not a one-size-fits-all approach. Somebody very young, we don't eat a lot of stem cells. We don't eat a lot of growth factors. In fact, some people who are health fanatics, right, they eat well, they sleep well, they don't touch any toxins, they work out all the time. I mean, they are true health nuts. All you have to do is whisper a suggestion of go ahead and heal, and their body is all over it. Other people who are diabetic, who've been drinking a lot, who are really stressed out, they don't sleep well, and they're not happy people. It's really hard to get the body on board to heal. | ↗ |
| 100 | University of Helsinki | Translational Medicine - Connecting life sciences and medical research... | 8122 | | 5 | 55.3 | positive | 2:14 | Hi, my name is Usha and I'm studying translational medicine here in the University of Helsinki. I did my bachelor's in biotechnology from India and I'm currently working as a research assistant in Hartman Institute. I wanted to study my master's in, of course, such that it gives me a bridge between the basic life sciences and also the medicine side. But what's interesting about Transmed is that you don't really have to have a bachelor's degree, especially focusing on life sciences, because we have had many students who are from a completely different background. Many of the courses involves a lot of teamwork and also there are different kind of courses which are mixed together. For example, we have laboratory techniques and then we have the bioinformatics and statistics. And apart from these courses, we also have, for example, clinical rounds where we get to actually go and do a little bit of an internship kind of a thing in the hospitals here in Finland. And that is really good because it gives you a completely different perspective of the healthcare from the other side. The very like about Finland is that they promote interdisciplinary education. It's not always focused on one thing but then how all the people from different faculties and departments can come together and work. And another thing which I really like is to infidelent apart from your studies, you can carry out with a lot of different extra-curricular activities. And the best part is you get great for it and credits for it and then you can use that in your normal degree curriculum. Helsinki has a really good international student community and there are a lot of different events that you can participate in being an international student, which is really nice to get to know like the other international students and as well as the Finnish students and the Finnish culture or inter-enrollment. You | ↗ |
| 101 | Miltenyi Biotec | Webinar: Stem Cell Reprogramming | 3426 | 48 | 4 | 55.3 | positive | 32:40 | [Music] I will tell you today something about the introduction uh or I will introduce about the foundations of stem pramming and will try to give you insights into the newest and the most efficient methods for this so let me briefly go into um the agenda for today first I like to start with an explanation what stem sets actually are uh then I want to introduce the technique of reprogramming and uh tell you what it is used for uh I will introduce different reprogramming techniques and we'll go further into detail for one technique namely the MRNA reprogramming and the last point for today will be the verification of ipscs so let's start with the first topic what are stem cells so when we talk about a stem cell what do we mean by that term stem cells are defined by two characteristics the first is their ability to self renew that means that they are able to create an identical copy and this way they can be maintained in a culture so they build a constant pool of stem cells for regeneration the second ability is the capacity to differentiate into specialized cell types usually progenitor stages that are more restricted in their developmental potential and will then differentiate into further specific lineages so here I want to describe shortly um the development of an embryo and show where to obtain embal stem cells um so the whole story begins with an oversight which is fertilized by a sperm the next step in the development will be the formation of a morula and then the next step will be the formation on about day 4.5 of the plastoy and this consists of an outer cell layer here um symboled by these yellow cells and also a blue uh symol Inner Cell mass and from this Inner Cell Mass you can can um separate embryonal stem cells so these blue cells are the embryonal stem cells and these embryonal stem cells have or has a special feature that they can differentiate into all the lineages of a body for example they can differentiate into cells of a circulatory system or the nervous system or the immune system and if you follow this whole process of development then this is what is described as differentiation I also want to uh introduce other terms to you which you will face if you uh are going more into detail for stem cell research um there are different features uh of different developmental stages and the first um feature is the toy potency which describes the ability to form all tissues in the body and the CL Center and this is a feature the Mora has for example and this means that all cells inside the Mora are able to not just form the embryo itself but also extra embal tissue if you go further in the development the next uh feature will be the PLU potency and this is the ability of the embal stem cells the ability to form three germ layers like here displayed the next um feature is the multi potency and this um or this is the term for the ability to differentiate into multiple cells or tissue types the so-called progenitor cells and an example for this is um are the hematopoetic stem cells which can form um uh different cell types of blood but nothing else and the last feature in this development is the uni potency which describes um The Limited differentiation potential into just one cell Lage the so-called precursor cells so as you have now learned where to find stem cells in Vivo how can we produce PL poent stem cell or BL poent cells artificially here you see again what I told you before here we have the prepotent stem cells so embryonal stem cells abbreviated by ESC and they um can form these three germ lay uh germ layers of the body the ectoderm which consists cells of like skin and brain the mesoderm um which can form bone and blood for example and the endo which forms pancreatic cells and lung cells in this process from the cell cells to the differentiated cells is called differentiation and for a long time it was thought that these uh is a one-way Road where you could just uh move forward into a more differentiated stage but however especially with direct reprogramming um done in the yamanaka lab I will explain this to you later on in more detail and then it became clear that you can go back from a differentiated cell into and PR poent stem cell stage and this is um forming then or this process forms then the so-called induced port and stem cells here abbreviated by ipscs here I want to introduce a timeline to you about the most important um Publications about reprogramming and I just want to highlight two of them um the first is um that here uh the first evidence that reprogramming of somatic cells is possible was done in 1962 by John giren and he cloned frogs by transferring the nuclei of differentiated intestinal cells into amphibian o sites and and then pretty much later in 2006 the yamanaka lab found out how to mimic this process with transcription factors and maintain these cells in a PL poent stage so ipscs behave like esls for example in s renewal and PR potency but also show a similar morphology also proliferation Gene expression and epigenetics so why are IPS cells now so attractive because they become um for example the ethical challenges of an es cell as you always have to destroy the embo if you if you isolate the inner semas of the plastoy and these IPS cells are especially interesting to the field of regenerative medicine as it's possible to reprogram patient specific um cells for example of a skin biopsy and they get can get then further differentiated um to study genetic diseases and screen for thetic compounds to find drugs because I promise you it's pretty much better to kill the cells uh with non-working drugs than killing the patient the other way around you can also use if you have a known uh disease mutation you can take this patient specific IPS cells to repair this IPS cells then further go on with differentiation then you have your healthy cells and this you can use for Trans uh Plantation into the patient and uh this eliminates the danger of immune rejection so this slides uses the so-called warington landscape to show the difference between cell States as a sort of an activation energy concept so once the same moves down the slope it differentiates and cannot go back in their normal development so here you see the second differentiating cells and it goes a different way and however as shown with the second ball we programming bypasses this and sends a cell to prow potency and note uh the ball is not shown to travel back along the same path it it tooks to differentiate so you would never exactly know where your cell is in this landscape how this reprogramming process is working in detail is not completely unraveled today but here I want to make it a little bit more clear at the top of the picture the whole story begins with the application of the four transcription factors op four so 2 kale of four and simic and this destabilizes the somatic cells in this case here FR plus and then a big case is occurring a lot of cells begin to do things which we don't want them to do other cells uh begin to establish certain expression profile FES and just a few number of cells and in this um this ass symbl by the spotter neck over here um just a few number of cells starts to establish the expression profile we wanted to have a whole Cascade of protein expression starts while the epigenetic landscape of the cells change and if this occures and the transcription factors shown here are expressed the reprogramming is done and the sematic cells transformed into an IPS cell so let's go for the third Point uh which reprogramming techniques do we have so I just briefly introduced to you the first technique which was the first evidence that sematic cells can be re pramming uh reprogrammed which has been published in 19 uh 62 by the G lab and he performed nuclear transfer from differentiated intestinal cells um into amphibian Ides which leads to uh cloning of frogs and they showed that all genes needed to make an organism are present in A specialized cell so this was maybe you know the story uh this was also done um with a cheap Dolly so just the cloning of an animal um the next method is the sell Fusion which is an alternative approach to reprogram the somatic genome which involves the creation of hybrids between somatic cells and other cells that contain reprogramming activities and um the special feature is or um the advantage is that the pro poent phenotype seem to dominate also in somatic sets so if they uh divide over here then always um the prepotent phenotype is um obvious but unfortunately it has been shown that this method is very inefficient and the last method I want to introduce is the direct reprogramming where we have the introduction of a small number of transcription factors of the yamanaka factors and um then the cells are reprogrammed and this is now the gold standard to produce ipscs and we will go further into detail during this presentation so there are two different groups of method methods which exist for direct reprogramming one that includes carrier for the transcription factors that integrates into the genome so here here you see that so later on the genome is altered and one method that is integration free and therefore the genomic Integrity is maintained and if you want to go for clinical trials and therapy we of course should go for the integration free method to conserve the original DNA nevertheless I like to shortly introduce two important integrative methods first is the retr rers um which has been used by shanaka um but this method takes up to six weeks to uh form um IPS cells um partial reprogramming so we have two phases of reprogramming partial reprogramming generates class one IPS cells that Express survival trans genes and enog genous po potency genes and full reprogramming in so-called Class 2 IPS cells silences the vector as the endogenous genes maintain the pr poent stage thus retr Vector silencing serves as a beacon marking the fully reprogrammed poly poent stage uh the disadvantage is that you alter the genome and don't have any time any control about the dose and furthermore you don't know if uh the silence genes are reactivated in a later stage um also the efficiency is very low it's below 0.1% and here we have the second um uh method I want to introduce the piggyback transposon system which is a Mobi genetic element that transposes between vectors and chromosomes via a a kind of a cut and paste mechanism and during transposition the pgb transposes recognizes transpose on specific uh sequences located on both ends of the transposal vector and moves the contents from the original sites and integrates them into specific chromosomal sites but the special feature of the piggy transpose and different from the ret Rivers is that it's also reversible nevertheless it is in genetic modification and again we have no final control about the time and dose of the expression of these um transcription factors for the integration free delivery there are also different methods on the market and here I want to introduce two of them the first is where it is here the sendi virus which acts exclusively in the cytoplasm of cells and cannot enter the nucleus or alter host chromosomes and it is therefore fundamentally free of the risk um associated with um conventional viral vectors Sendai viral vectors also reprogram cells with high uh efficiency the disadvantage of using Sendai virus is um that they have relatively high costs compared to um other methods um the establishment of virus free IPS lines requires up to 10 to 20 passages depending on the cell line um and reprogramming conditions and you must isolate and clonally propagate at least 10 primary primary colonies to establish only a few IPS sell lines per patient sample another integration free reprogramming method is the MRNA delivery and here uh it's very important um that you have the ability to reprogram stem sites using a method that is both non-integrative and nonrival and this is very important for future theerotic application and the advantage of this technique is that there is no risk for insertional mutagenesis that can later cause cancer and for CS that will eventually be used in the clinics this will likely be the dominant technology um also a big Advantage is that uh it's very fast this technology and you have a very very high efficiency about over 1% um for example MI a reprogramming can result in IPS cell colonies within two weeks but one disadvantage of um the MRNA reprogramming is uh the inconvenience posed by the daily mRNA transections required for this Method All right so let's go further into detail for this Mna technique uh waret Al published in 2010 how to generate synthetic highly stable Mna which can be used to reprogram ipscs and in their publication they showed um reprogrammed C colonies within up to se uh 17 days so this is what you see here I also want you to introduce uh our uh reprogramming kit the stemx MRNA reprogramming kit uh and we will see one typical workflow for mRNA reprogramming so we start the whole culture with um the preculture of sematic cells like for example fi blasts um in Repro Brew XF medium and then code plates with CTS and pl the cells on top allow the cells to adjust and on day Zero start with the transactions you will go on with the Trans affections for 12 consecutive days um also adding this b18r which was identified to enable increased Sur viability during uh RNA transection and on day 11 after the 12th transaction we stop with the transactions and allow the ipsc colonies to grow then we come to the point where we change the medium to to IPS Brew medium and um IPS Cy colon is are visible and I want to do that with you uh more or less live and this is what you would see through um the fluorescent microscope on day one these are fiber blasts and they have been um transfected for one or two times on day one and the big advantage in our mRNA reprogramming kit is that we use egfp as a transaction control so if these cells are green florescent like you see over here uh this shows directly how uh how efficient this method is and you see more or less 100% of the cells are transfected so here you see day three um the morphol morphology didn't change uh they grew a little bit the celles but still they're more or less 100% green so efficiency is still very high this you can also observe on day five Cs grew nicely uh and here on day seven you see the first sign that the morphology is changing a little bit so here you have more dense Parts in your culture and on day nine it gets little bit more obvious here there are very dense parts and you see maybe that they are um there's a little bit enhancement of the size of the nuclei which is um um normal for is cells but still the efficiency is very high and then very obvious on day 11 this is what you want to get out at the end of reprogramming this is a nicely formed um ipsc colony to be sure for the plal potency of this colonies you can also stain them with OCT 4 uh which serves or which is a transcriptional marker for p poent stem cells and serves like a fingerprint to identify IPS cells and in this case you see very nicely formed green florescent colonies um to keep the IPS cells further in cure you have to isolate them from the differentiated cells because you always have uh as I showed you before a lot of uh different sh or uh other cell types in your dish and uh also IPS cells also dead cells and you just want to go on with your prepotent cells and um one method would be that you manually pick these cells and isolate them so it's very hard I can tell you to pick this um that uh PR poent cells as you don't really know if you have really uh portent cells or not as you just have your dish and uh they are not fluorescent or something like that because normally for a picture like this you have to fix your cells and then you kill your C so you cannot go on with further passaging um therefore you would pick all cells which have a PR poent morphology you would replay them and passage them further on but um a new technique or a new highlight in our product portfolio is um a Life Cell stain antibody U which you can see over here um and for this you don't have to kill your C and you don't have to fix your cell and you can directly under the fluorescent microscope see what you really are or want to pick um one additional problem is that you maybe assume one colony is monoclonal so just originating from one cell but as you see by this picture it's not every time the case the more efficient option to isolate uh the reprogrammed cells is to separate them and this is one very famous technology for miltin biotech um therefore we have the St 160 microbit kit for the isolation of mRNA ipscs and this is working like um I would explain now so you have your uh PR poent cells which are expressing tra 1 60 and we have um very very small micro beads uh which binds to the tr60 positive cells these micro beads are consisting of iron and uh if you put that sample with your pro poent cells and some other cells inside on top of such a column uh where is a steel ball Matrix inside and you place a column into a magnet then these um microb beats um attached to the cells will bind to the column and everything what it's what is not positive for Tron 60 will run through and if you later on release the column from the magnet um then the um uh the column is not mag magnetic anymore and will not bind uh the magnetic beads anymore and then you can also wash out your then positive sample and hopefully have just your trauma 60 positive cells and this we have done over here and also analyzed with our flow cytometer um what is displayed in this plots is um two markers are two markers at first TR 160 um for plor potency and here the epcam marker uh which also serves as a pre potency marker and here on the um on this part of the blot uh you see um cells which are negative for both markers here you see cells which are positive for both markers and here you see cells which are just positive for the epca marker and here you see cells which are just positive for the tri 160 and what we want to obtain later on are these cells so in the original fraction just after uh the reprogramming you have for example here um just 42% of PR poent stem cells and if you now place all these cells also with the negative cells on the column um you get out a negative fraction first of all so what is washed out and don't bind to the cell and uh here we analyzed um how much per poent C cells are still here in this uh fraction and we saw there's just uh very yeah very small loss of cells of 2% so and if we then um analyze a positive fraction we see that the cells are pretty much enriched uh about a value of 94% so these enriched cells you can then later on use to replay them and then you can start uh with a pretty much higher cell number which will fasten the experiments dramatically all right then we come to the last point of my talk today U the verification of ipscs so there are different functional essays of per potency first is the Embry body essay um and these Embry bodies are generated by esc's on nonadherent plates and this is very important in the absence of safe renal cyto kindes so they differentiate and after several days of culture um this is resulting in ID bodies which can be individually transferred and cultured further under conditions appropriate to Coke's development of various cell types and then stained for uh different cell type marker to obtain if they are really um able to form all the uh cells of the body and which which is the evidence that this cells are still important um the second uh essay is the teratoma essay um and teratomas are generated by injection of cells into nonobese combined imuno deficient mice usually intramuscular or under testicular or kidney capsules and after 10 till 12 12 weeks um or also a little bit longer um you have teratomas and and uh they can be recovered and analyzed uh using histological approaches to examine uh as well if you have all the different tissues uh inside all right that's it for the foundations of reprogramming let me briefly introduce where you can receive more support on getting an expert in your stem experiments so we offer a 4day stem set course in our headquarter in bbak in Germany and also in San Diego uh USA where you can learn theoretically and practically to perform a whole stem cell workflow including reprogramming cultivation and differentiation and um maybe you also want to um attend one of our next webinars and then we invite you very much uh to to come to our website milon biotech uh.com weinar or you can also find more trainings on our website under milon biotech.com trining so finally thank you very much for your attention please let me know whether there are any questions thank you [Music] he [Music] | ↗ |
| 102 | Master of Translational Medicine - UCB & UCSF | Master of Translational Medicine Program at UC Berkeley & UCSF | 1184102 | 35 | | 55.0 | | 3:05 | The Master Translational Medicine Program is a relatively unique educational experience. We're blending engineering and medicine and business to try to create the future of healthcare innovation. Being at UCSF in Berkeley, we are in this pit-tradee of ideas with a range that goes from basic science and business and law all the way to clinical practice. In this one year program, they get to see how ideas get formulated, how they grow. So being in the barrier, you're seeing the leading edge of healthcare technology innovation works and innovation in general. Deciding to come here was mainly because I love engineering and I love science and I love learning about the different technical devices on the market. But I'm also very interested in the business components and what really matters in terms of what will make a product successful. And how do you test it, how do you get it approved, who's actually going to use it. And so by coming to this program, I get to learn all of that side of things. Our students work on a real-world project. So we're saying here is someone who's trying to develop a new medical device or a diagnostic and we're going to embed them with that team and give them some real hands-on experience on a project that other people are actually trying to make happen. I'm on the Zordera team where we're working on an injectable implant for ocular delivery of therapeutics. I have noticed that there are different strengths that we all have that can be incorporated synergistically to accomplish our goals. One of our members is chemically oriented and knows a lot about how the drug products are acting differently and that's good for me because I'm geared towards how the flows and suffer managed on a more macro scale. So it's interesting to see how our experiences and knowledge bases can kind of complement each other. I had this idea to stop brain death and brain damage and cardiac arrest and stroke patients. And then I realized there's this program called the MTM in Berkeley and UCSF that could help you commercialize medical devices so it just seemed like the perfect sort of fit. Working with students has been amazing. One of the things that you underestimate when you're a student and I did was the value that you're actually adding to one of these startups. And what I've realized now being on the other side of it is that our MTM team adds huge value to what we do in our startup every day. We tell them that their work will decide whether our startup makes it or doesn't. It's a really interesting way to approach a company is by treating it like a capstone project. You approach things from a student perspective where you're learning. There's no doubt in my mind that this was the right place to come to if you wanted to start a company to create a medical device to get it to patients. The support in the Bay Area is unreal. For people who are looking to continue their education, I would highly recommend this if you're interested in health care and business and learning how all those different things blend together. | ↗ |
| 103 | NewBeauty Magazine | Unlocking the future of regenerative medicine | 279 | 5 | 1 | 54.8 | neutral | 1:26 | The hair follicle is truly emerged as the ideal cell source to save for the future of regenerative medicine. For listeners and viewers out there, who is this really for? What type of future uses are we talking about? Is it cosmetic? Is it medical? Is it longevity? And what type of person should be doing this? It's a fantastic question. And I'm going to try to keep it a concise answer, because honestly, there's a lot of different avenues where this is going to go. We've already seen the creation of applications using our own cryopreserved hair follicles in the world of aesthetic medicine. And so we recently launched and released the first opportunity to leverage your bank cells, which is actually capturing your hair follicle cells, your very own, and growing them in our laboratory. As they grow in the laboratory, we actually capture all of the molecules that are released from those cells as they're growing. And so this includes large matrix molecules, like collagen, and elastin, fibernextin, and agrican, as well as small growth factor proteins, like PDGF, a number of factors like IGF1 can go on with a very long list, VGF, but ultimately the things that stimulate our cells to grow, divide, and create matrix, or the things that create our skin and other connective tissues. And then on top of that, exosomes and cells are released. | ↗ |
| 104 | Oxford Parkinson's Disease Centre | Studying iPS cells under the microscope | 2483 | 42 | 2 | 54.6 | positive | 0:17 | Next shall main who is looking at some dopamine neurons that she's developed from people with Parkinson's and PSLs. | ↗ |
| 105 | WKYC Channel 3 | Regenerative medicine: Using your own body to heal itself | 820 | 7 | 1 | 54.6 | positive | 1:44 | Regenitive medicine is a very broad field that's been advancing at warp speed. In some aspects, it actually uses technology to help our bodies heal itself. You've likely heard of stem cell therapy. What if it could actually cure your achy joints? Wouldn't that be nice? Seeing your health correspondent Monica Robbins takes us inside the science that believe it or not, is already inside our bodies. These are pretty incredible and the concept of using ourselves to heal ourselves is not new, but it's certainly advancing. Just as technology continues to advance what we do in the lab and biologically continues to advance as well, our ability to harvest and grow your own stem cells and then help to talk to those stem cells to have them grow cartilage or decrease inflammation or help a ligament heal better is what we're doing right now. But maybe next on the horizon is using stem cells to cure arthritis in your joints. We're currently in process with our FDA approved clinical trial to grow your stem cells for early arthritis or cartilage injuries. We've completed our phase one trial with remarkable results and we're looking forward to expanding that trial and hopefully in the near future it's available to all of our patients. And the future of regenerative medicine is now. Working with our implants and our different ways we help a graft or a ligament heal into the body continues to harness the body's potential to heal. And I think that's the most important part about regenerative medicine is we've realized there's nothing better than the human body and how the human body works. And so our goal now is to harness that to really improve an athlete's outcome. Monica Robbins, three news. | ↗ |
| 106 | HealthTree Foundation for Multiple Myeloma | What are Immunomodulatory drugs (IMiDs) and how do they work? #myeloma | 9323 | 103 | 4 | 54.5 | positive | 5:49 | What are imits and how do they work? Imits are immunomolatory drugs. There are class of drugs that are based on the first drug called Tolidamide and was approved a while ago. Now there's a class of drugs that is based on the same structure of Tolidamide, Lennelolamide and together they form the class of imits or immunomolatory drugs. And these drugs are old drugs that are very important cornerstone of most of the regimens that we use to treat multiple myeloma both upfront as well as in later lines of disease. And over time by tweaking the structure of the drug we have been able to develop more powerful compounds generally. And so we know very well from studies in the past that imits have a direct effect on the tumor and they sort of result in cell death and prevent the proliferation of myeloma cells. But very importantly the fact why we call the immunomolatory is the fact that they don't just have their effect on myeloma cells but they act very importantly on cells that consist of the so-called immune microenvironment of multiple myeloma. In the bone marrow so where the tumor is growing there's a lot of other cells of the immune system as well and we believe that they contribute or they can contribute to tumor killing and imits have an important effect on the cells of the immune microenvironment. More specifically we know that they activate T cells and NK cells, natural killer cells and both of these cells are known to be able to exert an anti-tumor effect. And I think that is part of the power of the immunomolatory agents. These are immunomodulatory agents that have been used in the treatment of myeloma and have transformed them. The first drug was thlytomide and interestingly the mechanism of action of these drugs was unknown despite very significant clinical activity. It is now felt that the major action of these drugs is most likely through a combination of targeting the myeloma tumor cell itself but most importantly also the tumor environment. The targets that have been identified and electrically have been cereblon as well as some zinc finger proteins such as Icarus and Iolus that are present both in the myeloma cells as well as in T cells and other immune cells within the microenvironment. But how exactly these mechanisms affect everything is not really fully invested at this point. So imits of course have a slightly controversial history prior to the discovery that they were effective in myeloma thlytomide was as a lot of people know initially used for morning sickness and pregnant women and obviously that had a terrible to radigenic or birth defect effects. It was later actually realized that this compound could have a beneficial effect in myeloma and it was tested in that arena and had some efficacy. Myeloma also has some nerve toxicity and causes psalmolins so its next generation agents let me a little bit and pome a little bit have less of these neurologic side effects and are very effective and better tolerated as well. As a class of drugs these drugs target both the myeloma cell and also immune cells. What they do is they actually lead to the degradation of specific proteins they are called Icarose proteins and those proteins that are degraded actually affect different processes in the myeloma cells that leads to the death of the myeloma cells then in the immune cells. In the immune cells they actually lead to further activation of immune cells and so in that sense that's why they are called the immunomodulatory drugs because they have this multiple immune effects where they lead to activation of natural killer cells and T cells that are thought to be important in part of the efficacy of these drugs. Are imits considered a form of immunotherapy? They can potentially be considered a form of immunotherapy. I think one of the challenges of that is that they are not necessarily clearly directed at the myeloma. It's perhaps more of a non-specific immune activation. Some of it made me myeloma directed some of it may not be. That is not very well understood I think at this point. How do imits target the microenvironment? Targeting the microenvironment I think there's become a bigger appreciation for the fact that the way to eradicate myeloma is through direct killing of the tumor cell itself but also of inhibition of the immunosuppressive mechanisms that exist within the bone marrow and microenvironment and also activation of immune functions that exist within the bone marrow and microenvironment. So for example there are suppressive populations such as myeloid derived suppressor cells. Non-suppressive factors such as bed jab or interleukin six or potentially even IL-17 that are known to inhibit the ability of the immune system to effectively kill myeloma. These are most likely down-regulated by the use of imits and then there are T cells that are known to kill and able to kill myeloma that have been shown to be up-regulated and to be able to kill more effectively when given or when exposed to a variety of imits. Lannolidamide and pomellolidamide as well as the newer imits. | ↗ |
| 107 | Foundation Fighting Blindness | Induced Pluripotent Stem Cells (iPSCs) Explained | 1247 | 22 | | 54.5 | | 2:04 | Induced pluripotent stem cells, or IPSCs, are cells that can become almost any type of cell in the body. Research and clinical trials are using IPSCs to study and potentially treat retinal degenerative diseases, including retinitis pigmentosa, usher syndrome, cone rod distrophies, and age-related macular degeneration. IPSCs are typically derived from skin or blood cells from healthy adult donors, or in some cases from affected patients. The skin or blood cells are then modified and allowed to become IPSCs. The IPSCs are a blank canvas and can be made into nearly any type of cell. IPSCs can be used for research or converted to other cell types to potentially treat disease. IPSCs are used in research to gain a better understanding of the causes of retinal diseases. Some researchers use IPSCs to generate retinas grown in a dish, which are known as retinal organoids. Researchers are using retinal organoids to study causes of retinal disease and to assess potential therapies. Cell therapies for retinal diseases use IPSCs that are converted into the cell types that are lost in disease, including photoreceptors and retinal pigment epithelial cells. IPSCs are also being used to create cell therapies. Cell therapy involves replacing cells that are lost or damaged due to disease with new healthy cells to restore function. When IPSCs are made from the cells of another person, it is often necessary for the cell therapy recipient to take specific medicines, called immunosuppressants to keep their body from rejecting the new cells. Cell therapy clinical trials are currently underway for retinal diseases, including retinitis pigmentosa, usher syndrome, cone rod distrophies, and age-related macular degeneration. To learn more and get involved, visit fightingblindness.org or scan the QR code. This video is presented by Blue Rock Therapeutics. | ↗ |
| 108 | Longevity Unlocked | EP 107: Stem Cell Therapy: What It Is, How It Works, and Red Flags to ... | 5 | 3 | | 54.2 | | 12:26 | There's IV compatible MSCs and there's non IV compatible MSCs and there's a difference between them. So if I inject you in the knee or the shoulder, I'm going to use a placento tissue. And that's me personally. There's other places that will inject the same stuff everywhere. But there is now used placento tissues. It's giant chantal tissue. We put that in your idea of killing you. Welcome to the Long Jebony Unlocked Podcast. We are your guide to optimizing your life, one health tip at a time. We are not providing a replacement for medical advice. Please always consult your doctor before making any diet, exercise, medical, or lifestyle changes. On this episode of Long Jebony Unlocked, Dr. K and I jump into what is a stem cell? What can it be used for? The different categories? How it's mainly a marketing term? And the red flags surrounding stem cell clinics. Ladies and gentlemen, welcome to Long Jebony Unlocked. I'm Coach Kyle here with Dr. K. Thank you guys for joining us today, whether we're talking about it. We're talking about stem cells. I still don't know what that means. What's stem cell? That's kind of part of the problem. I don't think anybody knows what it means because I'm not sure if it means anything. It really does and it doesn't all kind of at the same time. Yeah. So history lesson. Back in the 90s, the 1990s. Oh, back that far. Before half our listeners were even born. A guy named Dr. Arno Kaplan's working in the lab and he finds this thing. And this thing can do magical things. But he doesn't know what those magical things are yet. But he's like, I think this thing can do anything. And so he calls it a stem cell. And then fast forward to five, 10, 15 years later. Turns out what he found was not really a stem cell. He found what we now call an MSC. Keep changing the name, even though the acronym doesn't change. Medisinal signaling cell, mesenchymal stromo cell, mesenchymal stromo cell, mesenchymal signaling cell. He keeps just like, it's like Legos with the words. But basically what they are are a signaling cell that tells your body, hey, this is a lot of injury. Here's exactly how you need to fix it. It's like giving your body the cheat code for fixing. Because your body isn't that smart at fixing. It basically says it works through what's called Paracrine signaling, which means it sees a cell and goes, well, if I see that cell, then that cell needs to be the same type of cell. So put it there. Whereas these signaling cells say, no, no, let's have some order and some control. And like, let's actually fix these things. So that's what we commonly use. But then we can like muddy that water so hard because under the marketing word umbrella stem cell, we have placental adipose, umbilical bone marrow, amniotic, v cell, probably something else, random out there, mu cell, a couple others out there. They're like, what? Excel. Excel. Yeah, my arms aren't yet wide enough anymore, but like they're out there. But really, the main sources for them are umbilical, placental amniotic adipose bone marrow and fat. And from there, it differentiates further. Then we start talking about wort and jelly. Is a product, exosomes is a product, amniotic fluids of product, placental tissue, alligraft is a product, adipose tissue, alligraft is a product, bone marrow tissue, aspry is a product, v cells are a product, mu cells kind of falls under umbilical, but also sometimes adipose. And so you guys see how you're starting to get lost because everyone's lost. And I keep going. But really, what it is, different forms of these, we'll call them stem cells for the simplest. We're sitting in Florida. FDA, you can't get me right now. We're sitting in Florida. And the reason I say that is Florida is one of the first states to define the word stem cell. And there's like a whole disclaimer, whole advertising that you have to go through for it. But they've defined the word stem cell. So we're allowed to say stem cell because up until two years ago, you couldn't say stem cell. If I said stem cell enough times. I think if we use the transcript, there might be some good SEO benefits here. So there's IV compatible MSCs and there's non-IV compatible MSCs. And the difference between them. So if I inject you in the knee or the shoulder, I'm going to use a placento tissue. And that's me personally. There's other places that will inject the same stuff everywhere. But the reason I use placento tissues is because it's giant chunks of tissue. And if you put that in your IV, it would kill you because it would clog your part vessels. But when you put it directly into a joint, it actually becomes part of that joint. It fills the soft tissue defect. Whereas then there's IV compatible. And when you put them in IV, they will basically self-target towards areas of inflammation and go to work healing those organs by saying, hey, this organ's really injured. Come fix it. I'm hearing all these names and all these things, right? Stim cell is a marketing term. It's a catch-all for what could be dozens plus other things. And if you are using a doctor who's using, quote, unquote, stem cells and you ask them what they're using and they don't have a good explanation, that's probably a red flag. If they can't ramble like I can and then just utterly lose you, then yeah, they probably don't know what they're saying. I see a lot of this in like the Med Spa arena where they'll do a stem cell injection into the joint. They really don't understand the science. They don't understand what they're using. It could be the thing that should have been IV, but they put it in the joint and it's not going to work as well. I have talked to stem cell manufacturers who have literally stopped making joint injection products because they were worried that people would inject them IV and kill people. So there's a lot of misinformation and general lack of knowledge in the space surrounding stem cells and stem cell therapies and how they should be used, which product should be used. That's a 10,000 foot view. Is there anything else you want to go into? I mean, this was so far, I formed an episode. It's probably add something. I mean, fair enough. If we want to look at the best sources of stem cell, like why do you choose adipose over umbilical? So let's break this down into a little bit tighter of a grouping first. So placental traditionally is exosomes. Exosomes, they're not amazing at healing, but they're very good at reducing inflammation and so the only time we personally use exosomes is if you're doing them right before MSCs to help target the MSCs better. I don't really like standalone exosome treatments. You can do them if you really want, but I'm not a huge fan of them as a standalone. I don't think they're powerful enough. The reason a lot of places offer exosomes and they're so popular is they are much cheaper to acquire than MSCs. And so a lot of medspasers are doing them because they either can pump their margins or they could offer them for less later. Then there is, there's two different places on the market to really get IV MSCs, which is the MSCs, which traditionally is them. So umbilical slash orange jelly, it's same thing, and adipose. And so the reason I switched to the adipose derived IV is because I started doing it. The first thing I did, I tried it on myself, I was like, wow, this stuff, you can actually feel it. Like you feel it almost instantly. And then I started doing on patients. I was like, hey, this is a new product trying out, but you want to try it? And patients start telling me, hey, I'm feeling like lighter, more clear headed, like within an hour or two of doing it, which I'd never really seen before with the umbilical cord. And so that's why we switched to the adipose derived product. I just got better results. And then when you look at the research for it by nature, when your body makes an MSC for an umbilical cord, it's designed by nature to live for six to nine months because that's all it really needs it for. But when you take adult to arrive, and we're talking like 18 or 30 year olds, when you do an adult to arrive at MSC, it's designed by nature to live for years and keep off-plating growth factors. And so you get longer lasting results out of doing that adipose. So that's why we do that. And then there is again joint injections. So I could use an IV compatible MSC, and you're going to get some anti-inflammation, and it's going to get some signaling factor for healing. But what I do is a placental tissue derived, again, it's chunks of tissue. So when I inject it into your torrentendent, it literally fills that defect and solidifies it. So you get basically much stronger, longer lasting results. Yeah, so instead of putting MSCs, IV MSCs into the joint, and hoping that they have a strong enough signal to have your body repair it by itself, we basically put the raw materials of the repair in there and let your body just build it out. Integrate it. Who's a good candidate for IV? If you're over 18 and breathing air, you're great candidate for it. The reason for that is every time you do them, they're going to go somewhere and heal something. What is aging really? Aging is just like injury and destruction of organ tissue, your heart, your lungs, your liver, your pancreas. You name it as we live, those cells reproduce, and sometimes those cells reproduce improperly, and they stop working, and that's aging. So when we do IV stem cells, they can actually clear out dead cells called senescent or zombie cells. So they actually help you get rid of a bunch of dead cells and they actually help repair some of your active cells to basically de-age the organs. Yep, I've seen this a lot with my mother actually has done IV stem cells pretty consistently once a quarter, along with some microneedling therapies, but she looks like she is aged backwards like 15 years in the last couple years. It is wild. Is there anyone who isn't a good candidate? Active cancer, no. Pregnancy, no. If you're actively having a medical emergency, no, go to the hospital. Don't call me, just go to the hospital. Those are really the high-ticket ones. Also, if you're in the process of doing a ton of heavy clean out, you may want to reconsider. The reason for that, when I tell patients, because patients will ask me when's the best time to do a stem cell? IV, and what I tell them is, listen, all you can afford to do is one treatment ever, then wait until you're really cleaned out and your best shape possible to receive it. Whereas if we consider that they're basically free because for some people money really is no object, then we kind of do them progressively, maybe like once a month or so, because as we're cleaning you out, your body has to basically repair and rebuild that clean out. And so when we're constantly pumping in the IV stem cells, they're helping your body accelerate healing faster. That makes sense. So if you were to stack rank stem cell injections for joints versus PRP injections versus peptides, how would you rank those in order them in terms of power? Retreating like a true injury. Yeah. Like a torn, whatever. Tornaminiscus in your knee. So, torn mints in your knee is a great example. If it has not flapped over, which means it's basically torn so badly, it's flipped over on its head, if it's done that, go have surgery. But other than that, stem cells, 85, 9% time, one round of placental tissue alligraft is sufficient. If that's your only injury. PRP to help stabilize and, you know, it doesn't always create true imaging changes, but usually three rounds, sometimes four, it depends how badly that mints is torn, how far three, six, the, and then peptides, really the only peptide of the income is close is the BPC, TB500. That decreases inflammation and promotes mild tissue healing. That's like if you sprain your wrist and you want your wrist sprained to heal faster, it is not going to heal a truly injured tissue. It just won't. So does PRP, if you stack it with peptides, get closer to stem cells, or is it still just, could you stack these stem cells with the peptides? Absolutely. You can always add the peptides. It's just, I've never seen them create true tissue healing on their own. They just don't have that power ability. It's not what they're for. They decrease inflammation. Yeah. So it's a great adjunct, and if you want to boost your understem cell injection, it's great. But it's not, don't expect a fix based on peptides alone. That makes sense. What's the biggest red flag in stem cell clinics? We see this a lot now, and like, especially Florida. Where do you get your stem cells from? Whether it's through the testing done on yours, whether it's the ethics behind yours, extremely cheap. Like if someone offers you IB stem cells for less than like $1,500, question it. If someone trying to charge you more than $10,000, question it. If it's more than $10,000, they're charging too much margin. And if it's less than a couple thousand, basically it's probably not a good product or it's just so weak that it's trash. Yeah, that's probably what is there either getting like the cheapest, most lowest level stem cell available on market, or yeah, they're giving you like, they're dividing like, they buy one buy one, divide amongst like five feet. Because they're just the math doesn't math otherwise. Like if we're paying over $1,000 per mile, how are you selling it for 1500? That may be a sense. Okay. Any other things we should hit on stem cells? For injections, one thing I would say is if you're off by a millimeter, you're off by a mile, go back a few episodes. That's why we've bought a nanoscopes so that we can get even closer. But if you have people out there doing palpation guide stem cell injections, can I do a palpation guide stem cell injection? Yes. Do I have full confidence that I'm 1000% in the right spot? No, that's why I use an ultrasound. Okay, well ladies and gentlemen, thank you for joining us on longevity unlocked. I'm Coach Kyle. I'm Dr. Kay. We'll see you guys next time. This podcast is not medical advice and any information taken from this episode should be discussed with your medical provider and not be a replacement for consultation. We disclaim any responsibility for any possible adverse effects from information taken from the episode. | ↗ |
| 109 | Medical Appraisals | Regenerative Medicine: Stem Cell Therapy Explained Simply | 55225 | 31 | 6 | 54.0 | positive | 8:59 | What if we could not only treat disease but also repair what's broken, replace what's lost, and restore life where it once seemed impossible? Welcome to the remarkable world of regenerative medicine, a field that's rewriting the rules of modern healthcare. From stem cells to gene editing, 3D bio printing to AI, we're about to explore how science is enabling the body to heal itself. Let's begin at the very roots of regeneration. At the core of regenerative medicine lies the humble, but mighty stem cell. Stem cells are unlike any other cells in our body. They're essentially the blanks' late to biology capable of becoming skin, muscle, nerve, or even heart tissue. We've got for key types in the spotlight. Embryonic stem cells or ESCs are the all-rounders. Pluripotent and powerful, they can become nearly any cell type, but they're used as raised ethical questions. Adult stem cells, often found in bone marrow or fat, are more restricted, only transforming into certain types of cells related to their origin. Then there are induced pluripotent stem cells or IPSCs. These are adult cells reprogrammed to act like embryonic stem cells. Ethical and versatile, it's a win-win. Lastly, mesenchymal stem cells, the repair workers. These are masters of regenerating bone, cartilage, and fat tissue. They're already being used in promising therapies today. Now that we've met the stars, stem cells, let's explore how they're making a real impact. These aren't far off theories. They're treatments changing lives as we speak. In 2024, something remarkable happened. The FDA approved the first mesenchymal stem cell therapy for children suffering from a rare condition called graft versus host disease GVHD. These children had undergone transplants, but their bodies started rejecting the donor cells. Traditional treatments had failed. This new stem cell therapy? It gave them another chance. Real relief where hope had almost run out. Now let's go to China. A 59-year-old man with type 2 diabetes had his blood cells transformed into insulin-producing cells and then transplanted back into his body. In just 11 weeks, he no longer needed insulin injections. Imagine that a chronic condition managed through cellular transformation. It's not science fiction. It's regenerative medicine. Researchers in Australia are tackling childhood heart failure using lab-grown cardiac tissue patches. These patches, made from stem cells, are designed to integrate seamlessly into damaged heart tissue. Clinical trials are underway. An early results are full of promise, especially for children with congenital defects or chemothera-perrelated heart damage. One of the most incredible stories comes from Germany. A 7-year-old boy with junctional epidermolusis bullosa, a life-threatening skin condition, had most of his skin regenerated using his own genetically corrected stem cells. More than 80% of his skin was replaced. Not with bandages, but with fully functioning skin grown in a lab. So where do we go from here? Stem cells are just the beginning. Let's now explore the supporting cast of technologies that are amplifying regenerative medicine. Gene editing tools like CRISPR, Cas9, let scientists rewrite DNA with stunning precision. In regenerative medicine, this means we can correct faulty genes before the cells are transplanted, giving us a cleaner, safer, more targeted therapy. Imagine editing a cell to remove a genetic disease, then using that same cell to regenerate damaged tissue. That's the kind of future we're building. Now imagine turning those corrected cells into tissues, or even organs, with a printer. That's the promise of 3D bio-printing. By layering living cells and biomaterials, researchers are creating organoids, tiny versions of real organs used to study disease, test drugs, and someday maybe replace failing organs altogether. This isn't far off science fiction. It's already happening in labs, and it's picking up speed. To keep up with all this, we need more than microscopes. We need AI. By analysing massive data sets, AI can predict how Stem cells behave, what conditions work best, and how to personalize therapies for each patient. It's already helping researchers guide neural Stem cell development, a key step in treating brain disorders like Parkinson's or Alzheimer's. Put it all together, gene editing, bio-printing, and AI, and you've got a future where regeneration isn't just possible, but is precision-built, personalised, and powered by collaboration. But do these therapies work in real life? Sometimes the best way to understand science is through the people it impacts. Sarah's life changed in an instant when a spinal cord injury left her paralyzed. Additional treatments offered little hope until she joined an experimental Stem cell therapy trial. Doctors injected Stem cells directly into her damaged spinal cord, targeting the injury at its source. What followed was nothing short of remarkable. First came small sensations, then movement. Over time, and with ongoing rehab, Sarah began to walk again. Her story isn't science fiction, it's science in action. The powerful reminder that regenerative medicine isn't just about healing, it's about giving lives a second chance. Regenerative medicine is also making waves in the world of elite performance. Actor Mel Gibson, dealing with shoulder injuries and arthritis, turned to Stem cell therapy instead of surgery. The goal? To regenerate damage tissue and restore mobility. After treatment, he reported a significant improvement, less pain, more movement, and a quicker recovery than expected. His experience reflects a growing trend among athletes and performers who rely on regenerative therapies to bounce back faster and extend their active years. It's recovery redefined. So, we've seen some incredible breakthroughs, haven't we? But before we get carried away with the promise of regenerative medicine, let's take a moment to look at what might still be standing in the way. First up, ethics. Especially when it comes to embryonic stem cells, the debate is far from settled. For some, the very origin of these cells raises complex moral questions that science alone can't answer. Then comes the regulatory hurdles. While approvals, clinical trials, and safety protocols are essential, they also mean that a promising therapy in the lab could take years to reach patients if it gets there at all. And let's not forget the cost. Many of these treatments are still out of reach for large sections of the population. The technology is moving fast, but accessibility? Not quite as quickly. Finally, there's the unpredictability. How will regenerated tissues behave in the body five or ten years down the line? We don't always know yet, and that means continued monitoring, more trials, and a whole lot of patients. So yes, the road is promising, but it's not without bumps. Now that we've considered the hurdles, let's turn our eyes forward. What lies ahead in the world of regenerative medicine? Personalized medicine will become the norm, tailoring therapies to your unique genetic blueprint. Organ regeneration, once a dream, is becoming more real with advancements in organoid growth and bio-printing. Combination therapies, mixing stem cells with gene editing and bio materials will drive better outcomes. And global collaboration will be key. Shared knowledge means faster progress, fewer silos, and better lives. As we reach the conclusion, one thing becomes clear. Regenerative medicine isn't just a medical breakthrough. It's a shift in what we believe is possible. It's offering hope where there was none, and rewriting the future for conditions once deemed untreatable. But to truly realise its potential, we'll need to move forward with care, balancing innovation with ethics, progress with accessibility. Because in this powerful blend of science and human spirit, we're not just imagining change, we are building it. Thank you for watching. If you found this video helpful, don't forget to like, share, and subscribe to our channel for more valuable insights on appraisals, revalidation, and interesting topics in healthcare. | ↗ |
| 110 | All About the Immune System | What Is Immunomodulation For The Immune System? - All About the Immune... | 12 | 1 | | 53.9 | | 3:14 | What is immunomodulation for the immune system? Have you ever wondered how our bodies manage to fight, often infections while also keeping inflammation in check? This balance is where immunomodulation comes into play. So what exactly is immunomodulation for the immune system? It refers to the process of adjusting or modifying how the immune system functions. This adjustment can either enhance or suppress immune responses to maintain a healthy balance. The immune system is constantly on guard, defending us against various threats like infections and cancer cells. Sometimes however, the immune response can be too weak, leaving us vulnerable. Other times, it can be overly active, leading to damage to our own tissues, as seen in auto immune diseases. Immumodulation helps fine-tune these responses, promoting health and preventing disease progression. There are two main types of immunomodulation. The first is immunostimulation, which boosts or activates the immune response. This is particularly useful in situations where the immune system is not functioning well, such as during infections or in individuals with weak immune systems. Certain drugs can enhance the activity of immune cells, like tea lymphocytes and natural killer cells, making them more effective in fighting off infections or tumors. The second type is immunosuppression, which reduces or inhibits the immune response. This is important in cases where the immune system mistakenly attacks the body's own tissues, like in autoimmune diseases, or to prevent organ rejection after transplantation. Immunosuppressive drugs work by lowering inflammation and curbing immune cell activity, thus protecting healthy tissues from harm. Immunomodulators are the substances or drugs that bring about these changes in immune function. They can work broadly or target specific components of the immune system. For instance, some immunomodulators focus on particular immune cells or molecules like cytokines, which are proteins that help regulate immune responses. In the realm of medical treatment, immunomodulation plays a vital role in immunotherapy. This includes therapies designed to enhance immune responses against cancer cells. One approach involves blocking inhibitory pathways that tumors use to evade immune attacks. These are known as checkpoint inhibitors. Other methods use cytokines to stimulate immune cells or employ adjuvants to boost vaccine effectiveness. Overall, immunomodulation allows the immune system to be finely tuned for better defense and healing. By either amplifying protective functions or restraining harmful overactivity, this regulatory capability is essential for maintaining immune balance. It forms the basis for various therapeutic strategies aimed at treating infections, autoimmune diseases, cancers, and other immune-related conditions. | ↗ |
| 111 | Link TV | 'Cell Reprogramming' Wins Nobel for Japanese Scientist (LinkAsia: 10/1... | 1436 | 13 | 3 | 53.8 | positive | 1:14 | Japanese scientist Chinyayamanaka just received a Nobel Prize in medicine for his discovery that human cells can be reprogrammed. The Japanese stem cell researcher is sharing the prize with British scientist John Gurdon for discovering ways to create tissue that would act like embryonic cells without the need to harvest human embryos. Yamannaka celebrated the win but acknowledged his role as a scientist. This brings me great joy, but at the same time I feel a great sense of responsibility. stem cell research is still a very new field. Now on US Airwaves, a global channel of uncompromising stories, world news, documentaries, entertainment and culture. | ↗ |
| 112 | Hospital for Special Surgery | Regenerative Medicine for Muscle, Bone and Joint Health (HSS) | 38724 | 109 | | 53.7 | | 2:49 | Regenative medicine uses biologic therapies, which is a type of treatment that uses samples of person's own body or donated tissue to treat injury and disease. And these therapies can be used to improve symptoms and the treatment of certain conditions by enhancing the healing of muscle, bone, and joint tissues in the body. Now while we can't always reverse a condition completely, Regentive Medicine or Biologic Therapies can significantly improve the pain, the function, and sometimes may even help to avoid or postpone orthopedic surgery in patients that are the right fit for these kinds of therapies. These therapies often work through an anti-inflammatory effect. This means that they contain proteins and molecules that may have the ability to reduce inflammation in the body, which is often the cause of pain and discomfort for our patients. Two commonly used types of biologic therapies used in orthopedics are Plagelyrich Plasma or PRP and Cell-Based Therapies. PRP works by using a person's own blood and preparing a concentrated mixture, high in playlets, which are tiny cells that carry proteins called growth factors that help prepare damaged tissue. This mixture is then injected into the side of injury and PRP is currently offered for treatment here at HSS. Cell-based therapies involve the injection of living cells, usually coming from a person's own tissues. They are becoming increasingly popular in orthopedics. The two most common types use either bone marrow or fat tissue from the patient. Conditions commonly treated with these therapies include, Ophdarthritis and joint pain, Meniscus tears in the knee, Cardid genders, ligament sprains and tears, Candanitis and Tendinosis, and Label tears in the shoulder or hip. Because every patient's body is different, the use of a genitive medicine with therapies used in the patient's own tissue can have different effects on how the patient's body responds. In fact, studies are currently ongoing to determine how successful, regenerative medicine treatments are for a specific condition and a specific patient. All it is too soon to know. Research we are doing here at HSS suggested these therapies might not truly regenerate tissue, but rather they help in improving symptoms and inflammation processes. They may also help by delaying or even preventing some surgeries. There's now some emerging data to suggest that these biologic therapies can stimulate the body's own healing response. Regentive medicine is an ongoing treatment and may be considered a treatment option depending on the patient and their condition. Speak with your physician. We will evaluate your symptoms and medical history to see if Regentive Medicine is right for you. | ↗ |
| 113 | Canadian Partnership for Stroke Recovery | Regenerative medicine: an exciting new approach to stroke recovery | 15181 | 124 | 16 | 53.7 | negative | 5:11 | For years and years we were taught in all of our neuroscience textbooks that you were issued with a fixed number of brain cells when you were born and then over the course of your life they just died and over time eventually you know you would be losing thousands and thousands of neurons but it turns out that that's not strictly true The age of 21 my health was really really good. I was a competitive athlete all my life I was way at University of Waterloo doing my undergraduate degree and I went to the gym with my best friend on my 21st birthday and before we started working out I started getting some numbness in my left side kind of like my grades I typically had. This numbness wasn't subsiding so I said forget the workout let's just go as we were leaving the gym I collapsed had a big seizure and was rushed to hospital and found out that I had an AVM massive brain hemorrhage did not see the stroke coming whatsoever neurogenesis really refers to the formation of new brain cells After a stroke you get this rapid increase in the proliferation of the stem and progenitor cells the dividing cells within the adult brain so this is important because those cells have the ability to become neurons but what actually happens is that those cells migrate towards the side of injury from the stroke but very few of them actually survive that migration so they just don't get to where they need to be and Then when they're there we know that the environment around the stroke is not very good So those cells actually can't incorporate and become neurons on their own Obviously one of the questions we have in basic biomedical research is how do we increase the number that can form new neurons and how can we make these better integrate into the circuitry within the brain? For repair to occur you need to have the blood vessels regrow and the blood flow reestablished we know in and around an area of stroke There are a lot of cells that are hanging in there But they are starved for oxygen their star for nutrients and the sooner you can improve the supply the more likely they will be to survive so if Dr. Legase was successful in finding ways to promote their survival Then potentially you'll have a resource right there in the damaged brain that can be ready to Repopulate the area of damage with new nerve cells. We're still learning a lot about this phenomenon But it's conceivable that down the road Five years or 10 years we would find even better ways to harness this phenomenon and encourage greater proliferation and migration of new cells to areas that have been damaged in the brain and Really be able to restore some of the function that was lost because of an earlier stroke I heard initially that you only get certain recovery after so many months But here I am living proof seven years later and I still find changes and there's thoughts promising research coming up to you to look forward to One of the most difficult questions as a basic scientist that I'm asked is how soon are we gonna be able to see this come to the clinic It took a long time to understand you know, workings or cells that took a long time to understand what stem cells were how they worked How the the building blocks of life the DNA Works in terms of controlling cells, but in getting that understanding we have now developed ways that we can actually Manipulate these things and use them therapeutically. Yes, it's taken 20 years But it sometimes takes that long to really develop the tools that you need that we can use effectively in patients We stop the research if we don't try to understand more about what's happening within the adult brain There will be no future in terms of understanding how we can enhance patients lives after a stroke Someone like myself who has had a stroke seven years ago in his chronic It's very hopeful to me to hear that they might be able to prepare the damaged Cells in my brain in one day and we get the use back in my hands. It would be so life-changing So neurogenesis research it's something that's fairly new With respect to stroke recovery, but it has tremendous potential for restoration of function if we can continue to make the inroads that we're making at present We're entering that new phase. So I think regenerative medicine is moving out of it It's been almost purely a research phase into one that's going to have important and perhaps dominant clinical application You You | ↗ |
| 114 | Life Science Connect | Why iPSC is Research Thriving | 20 | 1 | | 53.7 | | 4:51 | All right, we have a lot to get through today, so let's get started. And I'd like to kick off our conversation under the scientific and clinical translation topic. And so to kick things off, Julie, I'd love for you to please walk us through why IPSE therapies have become such a compelling area of research and development and perhaps what makes this approach so exciting and why there are so many, why so many in the field are turning their attention to it as a potential, you know, game changer in the treatment landscape. Oh, Julie, I think you might be on mute. Thank you, Aaron. I'm really, really appreciate being here. I'm excited to be able to have the discussion today with you and Aaron Kimberl. And just want to say it's such an exciting space right now. There's a lot of groundbreaking advancement for regenerative medicine, biotherapeutics in general, especially at our center for regenerative biotherapeutics. We're working on a lot of different applications. But I think most of all, if you think about it at a high level, it's the versatility and accessibility of these cells, opportunities to not only use them as patient specific, but also an allogeneic source. The immune cloaking has really come along. There's a lot of applications. We see it moving into clinic for allogeneic use. And this is a game changer potentially for patients not to require immune suppression. I'm super excited about that. Not only in treatment such as diabetes, but also looking at tissue engineered organs in the future. And then targeting these complex diseases, looking at diabetes, multiple strokes, cardiac conditions that normally doesn't, does not have a specific treatment or a cure. So these cells can differentiate. It's very exciting looking at the diabetes space, possibly differentiate into beta, alpha delta to complete the islet is a huge opportunity. So I think it can have a global impact on patient health care. And it could be accessible, so democratized as a therapy to transform healthcare at a global scale. So there's a lot of interest in it, a lot of excitement, a lot of tools coming on board. And I think investors are extremely interested as well. Good, good, great. And a lot of what you mentioned today, especially the allogeneic approaches are definitely going to be part of our conversation. In fact, in leading up to today's discussion, our registrants have submitted some questions and some topics and the allogeneic approaches are certainly something they want us to cover, which we will. But before we do, Erin, I'd love to hear from you your perspective on why I, excuse me, IPSC therapies have become such a compelling area of research and development. And from your perspective, and your tenure, and even at Estellus, what are you seeing? Yeah, thanks for the question. First of all, yeah, thanks so much for your program and for inviting us here to talk about this. It truly is an exciting time. So I think when you look at the value proposition of using IPS cells as a starting material, their flurry coat in nature means that they have the ability to both self-renew and differentiate into a wide variety of cell type. And then, the new old property really means that you can expand them practically to unlimited amounts. So you have that same starting material that can be replenished. And then their ability to differentiate into all cell types in the body means that we have a great opportunity to develop a wide variety of therapeutic cell types, as Julie mentioned, so many different clinical applications. And I think that this is very helpful when you can have that consistent starting material from the same pool of cells. And you don't have to deal with the donor to donor variability or the exhaustion potential because you can simply go back and use that same replenishable starting material. So I think it's a really versatile tool that we can use for cell based therapies. And then in just thinking about the value proposition of cell based therapies, in many cases where tissues or cell types in the body have degenerated due to injury or disease, the only thing you can do to help patients in those situations is to replace the missing cell type or to provide a more sophisticated therapeutic entity. And I think there's a lot of advantages to using cells for patients with high-end metamine. | ↗ |
| 115 | University of California Television (UCTV) | The Idea Behind Regenerative Medicine | 13792 | 227 | 10 | 53.6 | neutral | 3:18 | The idea of regenerative medicine is how can we restore form and function of disease tissue through biological processes instead of just these mechanical and hardware processes. So regenerative medicine could just be transplanting human tissue. So this could be living tissue. We call that autograph. Take bone from one part of your body, transplant it to another, maybe bone from a part of your body that's not load bearing and so you could spare it, so to speak. You can also get dead tissues, so allegraft tissue. And so this is still classified as regenerative medicine because you're using the biologics. And it's probably the most simple form. The next one is cellular therapy. I'm going to cover this in less detail. This is a topic we talked about in our last many medical school as specifically stem cell therapy. There's also this idea of tissue engineering and we're going to talk quite a bit about tissue engineering and this idea of maybe re-growing an entire organ and how you might do that. Gene therapy. So if you have a disease that is caused by a particular mutation, can we go in and edit that particular part of the gene so that you can take out the bad DNA and put in better DNA? And so the last one is just can you inject something that will stimulate endogenous repair? So can you trigger the body to heal itself? So the goal of regenerative medicine is really this idea of can we capitalize on the innate regenerative capacity of bones and cartilage in our skeleton to learn from it but also to accelerate it or use it when we don't have when that natural tendency isn't there. So who knows what this animal is? There you go. The winning prize in the back is the axolodil. So we do look to the axolodil as inspiration for regenerative medicine. So this is one of the few species, Nathan correct me if I'm wrong, who can regrow an entire limb and not just heal it with scar tissue but actually regenerate a full limb. So this is a picture if you chop off the leg of this axolodil, it will slowly regrow. The fingers will reform, the muscles will come back, the vasculature will come back, it will fully regenerate. There are some things lizards and salamanders tails have the ability to regenerate to some extent but they often it's more of a healing response, not this full regenerative response. So the axolodil we can use as an example to study the molecular, cellular and genetic mechanisms that are regulating regeneration and then we can try to capitalize on those principles, those basic principles for human regeneration. | ↗ |
| 116 | CBS News | Special stem cell treatment for spinal cord injuries shows promise | 64675 | 435 | 42 | 53.5 | negative | 3:04 | An experimental procedure aimed at repairing spinal cord injuries is showing promise. It uses stem cells in the damaged areas in hopes of restoring function and movement. Dr. Don Lapouk has one patient's story. Dr. Don Lapouk has one patient's story. There's nothing we could have done to change that night. On April 9, 2013, James Mason was an accident waiting to happen. He had been drinking and his stepfather, Bob Gamboudi, tried to stop him from driving. He grabbed onto me, I grabbed onto him, pulled my leg out and we fell back and his neck broke. I remember just hitting the ground. I remember the whole way with the stretcher. The most devastating part of the whole process was the first day that he lifted out of a bed and nothing moved. Just his head. That really hit hard. At that point, I really wanted to go jump off a bridge. Mason was left a quadriplegic with just the slightest ability to move his arms. Dr. said he'd never walk again. Gamboudi, a retired cop, became his full-time caregiver and found an experimental trial at New York's Mount Sinai Hospital. We'll take good care of you. We spoke with Mason just before he underwent delicate neck surgery to try to repair the damaged portion of his spinal cord by injecting stem cells. And what's going on in your head? What are you thinking? What are you hoping for? I'm just super excited. I just get it done and go back to rehab and start proving the doctor wrong even more. Okay, well. The surgery performed by Dr. Arthur Jenkins took four hours. Researchers have followed James and five other patients all with severe spinal cord injuries. Squeeze as hard as you can. We met up three months after the surgery. Notice any change? Yeah, my wrist has gotten a lot stronger. I'm able to grasp around a lot of other things. And after another three months? I think it's almost doubled with how much I've gotten better and the sensation back into my feet. I can feel pressure onto them throughout my legs. And they've noticed that I have a little bit of movement into my hips now. Today, the company sponsoring the trial reported four of the six patients experienced improvement in both muscle strength and function. Try pulling the thumb towards me. Dr. Jenkins, who is not affiliated with the company, has continued to monitor Mason. My two senses, it worked. That this actually changed his neurologic recovery and function. That his actual functional improvement is from the stem cells that were injected. Mason does not blame his stepfather for the accident. In fact, he's grateful. If I'd gotten in my car, I could have killed someone else, someone's mother, someone's father, someone's child. I wouldn't, if I would have survived through that, I wouldn't have been able to live with myself with that. It's tough and people say, oh, I'm sorry. Don't be sorry. I still have him here. Mason believes the stem cells accelerated his recovery, but it's hard to know what would have happened without them. More research will be needed to try to establish whether they actually repair damage to the spinal cord. Dr. John LaPouque, CBS News, New York. | ↗ |
| 117 | Anu Test Tube Baby Centre | Decoding the link : Immunomodulation and invitro fertilization (IVF) | 444 | 12 | 1 | 53.5 | negative | 4:24 | Hello friends, I am Dr. Anurada, Patelitis Specialist from Anu Bestu Baby Centre, Hyderabad. We are going to discuss the role of immunomodilitary properties of registrant for successful IVF cycles. Most of the IVF cycles utilize control ovarian stimulation protocols which require bono-rotropping releasing hormone analogs. The use of GNRH analogs causes pituitary suppression leading to a dysfunction of the dysfunction of the purpose of lithium and reduced progesterone levels in the luteal phase. So how do you recognize the luteal phase deficiency? Which can be detected by low progesterone levels, delayed and novitual secretary trans commission and a shortened luteal phase of less than 10 days, resulting in reduced embryo implantation, low pregnancy phase and increased miscarriage rates. So, this necessitates a luteal phase support to enhance the probability of continuation of pregnancy in IVF cycles. In the luteal phase, endogenous registrant induces a secretary trans commission of the endometrium after adequate estrogen priming and improves endometrial receptivity. The reduced endometrial receptivity would cause a lower impractation rates and low success rates in IVF. In pregnancy, the maternal immune response is modulated away from the cellular that is a TH1 response and towards human eliminated that is TH2 response to produce antibodies. In addition, cytotoxicity mediated by non-specific natural killer cells is dampened by the inhibition of TH1 cells which produce cytokines such as interleukin-2 and interferogama. Activation of NK cells is known to result in fetal resorption. Thus, there is a bias towards the production of TH2 cells in pregnancy, which may be a productive mechanism to promote fetal survival. Dihydrogen strong is a progesterogen which is potent, oral active and is similar to endogenous progesterone in its molecular structure and pharmacological effect. It acts via the progesterone receptor to produce a 34kd mediator protein called progesterone induced blocking fracture, that is PI-BF, which mediates the immunomodulatory effects of progesterone during pregnancy. Progesterone induced blocking factor also induces the TH1 TH2 pregnancy protective cytokinescence. Moreover, PI-BF suppresses NK cell activity by inhibiting, perfuring exo-cytosis and increases the synthesis of asymmetric antibodies that can mask featureally derived antigens without activating the complement system, phagocyteosis or cytotoxicity. And therefore, plays an essential role in the immunological defense of the fetus. So to conclude, hydrogesterone induces an embryo protective immunovodulation, inducing to the success of pregnancy. I have been using hydrogesterone for the last 25 years, for most of my IVF patients, my name for the LIT patients, unhesitantly and confidently, unless there are some contraindications, or if the patient is not able to tolerate the drug. The next session will be on maintaining TH1 and TH2 balance and its impact on IVF substance rate by my fellow colleague. | ↗ |
| 118 | The Dan Buettner Podcast | Reverse Your Biological Age: New Research Shows Fasting Could Make You... | 3243 | 80 | 15 | 53.4 | negative | 1:10:35 | No transcript | ↗ |
| 119 | Twist Bioscience | Cellular reprogramming for the scalable production of human cells | 2485 | 50 | | 53.4 | | 36:32 | hello everyone my name is ernie guzman i'm the manager senior manager of technical support at twist bioscience and i'd like to welcome all of you to today's presentation entitled cellular reprogramming for the scalable production of human cells presented by dr michael d'angelo senior scientist at bid bio just a couple of quick housekeeping rules to cover first is that all lines will be muted during the webinar and this is to reduce any distractions during the presentation secondly we will have a q a session at the end please submit your questions in the q a box we will answer your questions after the presentation is complete and finally following the presentation there will be a short one-minute survey that we would really appreciate you taking your feedback will help us improve all future webinars and now i'd like to introduce our speaker today's speaker is dr michael d'angelo michael is a molecular biologist and genome engineer he leads the bit bio team conducting technology development and gene editing projects which are at the core of all of bitbio's cellular reprogramming activities and with that michael the floor is yours you so much for that introduction ernesto and i'd like to thank twist bioscience for the invitation to speak today on behalf of bit buyer today in this webinar i'd like to tell you about the need for better human cells and the promise of cellular reprogramming i'll tell you about the bios approach to making human cells and how twist gene synthesis has helped us and i'll finish off by showing you some data and showing you uh some of the products that we've made using our optix technology so why do researchers need human cells well human biology is often different from the animal models and tumor cell line models used in pre-clinical drug testing and as a result many drugs often fail in human clinical trials because of a lack of efficacy or toxicity that was not appreciated using these non-human or non-physiological human cell models so where research is going to get good human cell models for drug testing or you might think that the perfect human cell model would be primary cells from donor tissue however these have some problems they are of limited source because they need to come each time from tissue donations and they often display highly variable biology because they need to be isolated from complex tissues and they come from donors with different genetic backgrounds adding you know heterogeneity and noise to the system there's also classical tumor-derived cell line models these have advantages because they're easy and simple to grow however they don't they're transformed and they don't represent normal human biology and then you've got pluripotent stem cell derived models which in principle have the ability to provide an unlimited source for human cell types at the moment however their bottleneck is really realising their potential and at the moment all of these three sources suffer from a lack of consistency scalability maturity and purity so if i tell you a little bit more about ips cells so these are cells that have been reprogrammed from mature human cell types back into a pluripotent state so that they're very similar to embryonic stem cells in their ability to differentiate into all the three germ layers of the human body and in principle have the ability to become any cell type of the human body and so they have advantages in that because depending on where you get that starting cell type from they have the ability to um represent different human genetic diversity they are self-renewing and therefore they're inherently scalable and they are now have really robust cell culture procedures in place which means that they're amenable for genetic engineering and so what we really want to use however is these cells on the right over here so we've got a neuron or white blood cells and red blood cells for example we want to get to a mature cell type from these potent stem cells and the traditional protocols for doing these are called directed differentiation and really with these protocols what you're looking to do is mimic development in the dish so you're putting generally growth factor combinations on the cells to mimic what happens during a regular developmental pathways via various intermediaries and and precursor cell types to end up at the final mature cell type that you're interested in however these tend to suffer from having very complex protocols with very expensive and complex media that needs to be prepared and therefore they struggle with scalability also the maturity and the purity of the final cell type you end up with is not always particularly where you want it to be and so synthetic biology provides us with a new paradigm for how to make mature cell types from pluripotent stem cells and this is the idea of reprogramming so now instead of the cells having to interpret a complicated extrinsic signal we're now giving them a strong simple to interpret intrinsic signal by over expressing transcription factors and in this case we're imposing the cell identity and transcriptional network upon the cells and therefore speeding up the differentiation process however standard reprogramming methods lead to polyclonal heterogeneity and low scalability and this is where our opto x technology at bitbio comes in and we're able to now get cells at the end that have high purity maturity scalability and consistency so what are we all about at bitbio so bitbuyers mission is to code cells to advance the well-being of humanity and to do so we apply the principles of computation to biology our current focus is to develop a scalable technology platform capable of producing consistent batches of every human cell type and to enable research and drug discovery to move on from less efficient models and work with the cells that are actually affected by human disease and the scalable platform of consistent cells will also be the basis for a new generation of cell and tissue therapies so at bitbio we have two pillars on which we're based so in order to reprogram cells we need to identify the optimal transcription factor code that can reprogram cells from the pluripotent state into the mature cell type of interest and to do that we've built our bit bio discovery platform and this is a platform that allows high throughput experimentation coupled with machine learning to determine the optimal transcription factor code of interest that we can then use to program a mature human cell type of interest and then once we've identified the optimal transcription factors they are then ready to be put into our optix platform which is the way by which we over express the transcription factors needed for cellular reprogramming into the new cell type of interest and i'll go into detail about how the optix platform works on the next few slides what this allows us is to have cells that now have very high consistency very quick uh speed to maturity high scalability they're very easy to use and cost effective so optics stands for optimized over expression and so older methods for example using lentivirus or so non-specific integration methods lead to high variability in reprogramming and this is because they each gene expression cassette will land in a different genome location and therefore leading to differences in expression level of the transcription factors and therefore differences in the outcome of the reprogramming so initially experiments were done using a targeted system so into a genome safe harbour site using an inducible system so in this case the doxycycline inducible system uh however when this was at first uh tested what was seen was low expression and silencing of the transgene in this case gfp so you can see patchy and low expression in this ips colony here and so from this is where optix was developed and so in a seminal paper from our founder dr mark cotter's academic lab what they did was a simple trick what they did was to split the two components of the doxycycline inducible system so we have a constitutive expression of the rtta transactivator protein from one genome safe harbour site and then add a second genome safe harbour site we now have the uh tetracycline response element uh inducible promoter driving expression of the transgene of interest and now what you see is strong stable expression every cell in this ips colony is now expressing gfp and so optox is able to overcome these limitations of silencing so this is great because with the inducible system what we have is in the absence of doxycycline pleuric potency is sustained and so these cells are now self-renewing and inherently scalable and now when we add doxycycline we have deterministic induction of a new cellular identity and so these are examples from this paper showing reprogramming into these three cell types of interest in very short time frames and so this is what it looks like in action this is a time-lapse image of cells differentiating into glutamatergic neurons what you can see is that within just three or four days they're already displaying neurite outgrowth and then they've become post-mitotic and they form a dense neural network within a week so what's really exciting about this is the speed at which they're able to form such a dense neural network this normally takes weeks with classic directed differentiation cultures and also the homogeneity that you can see really every cell in that culture is reprogramming they're changing morphology at the same time and the resulting cell population is extremely pure so how has twisted synthesis helped us in our mission so in order for us to get access to different transcription factors that we want to test with the op2x platform we use twist gene synthesis and so what we used to do was when we had a new transcription factor we would get it synthesized in the twist cloning vector then they would send it to bitbio where me and my team would then perform sub cloning into our updx vectors however now it's even better we've completed custom vector onboarding so they now have our targeting vectors there and what we can do is whenever we want new transcription factors to be tested we can order gene synthesis and twist will clone them directly into our into our optics vectors and ship them back to us ready to use so this is fantastic because it's fast and it frees up the time that my team would have spent at the bench doing the doing the cloning it's also inherently scalable because if my if we were to order a large number of transcription factors well the amount of time that we would take to sub-clone them uh would scale somewhat linearly with the number of factors that we ordered whereas at twist it takes roughly the same amount of time to get one transcription factor as it takes to get 50 because of their high throughput platform and we're also really excited to take advantage of their new higher yield dna prep offering which will hopefully get us access to transfection-ready dna so we'll spend even less time at the molecular biology bench and more time doing exciting things uh plugging these into ips cells and making exciting new human cell models so bit bias cellular reprogramming is really making a new benchmark for human cell models due to the high purity the speed of differentiation the consistency not only batch to batch but really cell to cell in each vial and also the scale at which we're able to do production and this enables a number of applications for basic research both normal and disease models and we're really building up a great capacity for genetic engineering of disease models and this is enabling for developmental and cell biology experiments it's also enabling for drug discovery so both normal and disease models can be used for high throughput drug screening target discovery and high throughput toxicology screening an interesting application is in bioproduction and actually our founder mark cotter is also a co-founder of a clean meat company using the oc2x technology in cells derived from livestock animals to make a scalable source of lab-grown meat and of course a really exciting application for this would be cell therapy whether it be immune cell therapy or other regenerative medicine applications for different cell types so now i'd like to show you some data from some of our human cell models and so these will be our ips derived neurons and myocytes so first up is our fully launched product which is the human io neurons glute product these are ready for experiments as early as two days post revival and they are a majority are glutamatergic neurons a something like 88 and a smaller subpopulation of cholinergic neurons so what you can see here is some immunofluorescence staining for pan neuronal markers beta-3 tubulin and map2 and then in orange here are the two glutamate transporters which are specific for glutamatergic neurons v-glute 1 and v-glut2 bulk rna-seq analysis has shown that the neurons have a rostral cns identity they exhibit robust neurone outgrowth and form functional neural networks in as little as 17 days that demonstrate drug response so what do our customers get so at bitbio the first phase here is performed which is induction so for three days the cells are primed towards the neural fate and then their cryopreserved and then you will receive one of these cryovials over here with cells that are ready for ready for plating and rapidly mature upon revival and then it's a very simple process in the customers hands they go through a very they go through a four day stabilization phase during which doxycycline is kept in the media and then a maintenance phase for however long you want to culture them where doxycycline is now removed and during that whole time they've just got a simple glutamatergic neuron media which is sim is a fully disclosed formulation and it this is enabling for our customers to customize it for their particular experiments so we've done some deep characterization on these cells so we've done single cell rna sequencing so what you can see here is a time course of reprogramming so following anti-clockwise from the ips state through some early time points here 12 24 48 and then 72 and 96 hours and then also some very mature cells over here two and two and three weeks and what you can see is the pan neuronal marker map t starts to come on around that day three to four mark and then he's really expressed in every cell at the two to three week mark and most of the cells are expressing this v-glute glutamatergic marker with a smaller population that express this this cholinergic neuron marker and so our partners charles river have used these cells in various different experiments you can email us for a copy of this poster if you're interested at info at bit.bio so what they've performed are some functional characterization using high resolution multi-electrode arrays so that is showing that the cells demonstrate electrical electrophysiological activity and so um both at two weeks and then increasing at three weeks in culture the firing rate percentage of active electrodes and the spike amplitude all increase and also they have validated these for high throughput assays in 384 well plates and so if you're interested please email us and we can give you a copy of these this poster and now i'd like to talk to you about another cell model that we've created which is the skeletal myocyte so iomiocytes skeletal this is in beta testing phase and will be hopefully launched soon but if you're interested in being on the beta testing being one of our beta testers please get in touch these are also ready for experiments as soon as two days post revival and contractility can be assessed as early as three days post revival they exhibit visible striated fibers and multi-nucleated myotube formation by day 10 in culture and uh what you can see here is immunofluorescent staining demonstrating robust expression of components of the contractile apparatus including desmond dystrophin troponin and titan and also we validated by qpcr the expression of key markers including various myosin heavy chain isoforms as well as the transcription factor myogenic and so here we have a video showing spontaneous contraction of these cells so this is in the absence of any stimulation 15 days post revival there they go always freaks me out when i see that down the microscope and importantly also these cells if you add a stimulus such as acetylcholine these cells contract very strongly then so what i've shown you is data from our i o neurons glute fully launched product and coming soon our imi site skeletal and also before the end of the year we expect to launch our io neurons gaba which is a gabaergic neuron product as well as our io glio ioglia oligo product which is a human oligodendrocyte cell model and if you're interested in those please get in touch and we can let you know when they're going to launch so at big bio we're developing the next generation of human cell models and providing the best cells for research and drug discovery and our cells are used in research and disease modeling they've also seen applications in in 3d printing into 3d scaffolds and so there was a recent paper out of oxford university using our cell using our neuron cells in a 3d printed cell scaffolds and also in high throughput screening and at this point i'd like to thank our partners charles river who are using ourselves in high throughput in their high throughput screening applications and abcam who where ourselves are available for purchase if you want to go to the ad cam website you can find the cells available there and if you are an academic researcher or working in a not-for-profit organization please make sure you take advantage of the discount code there so that you can get access to our sales for a really great price so bitbio allows for the scalable and consistent generation of defined human cells and the development of the bit bio lineage portfolio portfolio is driven by our discovery platform for the identification of novel and optimized transcription factors for new cell type reprogramming and our optio x technology for the controllable expression of transcription factor combinations and all of this results in cells that have high consistency high speed to maturity scalability ease of use they're cost effective and they show really high purity with that all that's left is to thank the team at bitbio that really make it a joy to come to work every day um the one problem with fun jumping pictures is that i think all you can see of me is maybe my shoe right there behind my boss who's blocking me but it's a fun picture nonetheless and yeah thank you again to twist for inviting me to give this webinar today and with that i think we'll take some questions uh thank you michael for uh your presentation really appreciate it and now we'll take some questions from the attendees um as a reminder if you have any questions please make sure to ask them in the q a box um so a couple of questions here how does the opti-ox improve reprogramming so reprogramming the cells is by directly activating a program that defines particular cell identity by over expressing a transcription factor from within however typical methods for over expressing transcription factors leads to heterogeneous expression and therefore variability in the final cell outcome optics gives us source where every cell is expressing the transcription factors at the same time and at the same level and therefore what you end up with is a highly consistent reprogramming it is a highly consistent reprogramming event okay another question so you've shown the power of the optio x generate mature glutamatergic neurons and skeletal myocytes uh what are the applications of your human cell models and is bit biodeveloping any other cell types yeah so defined and consistent ips derived cells provide an excellent alternative to animal models and immortalized cell lines which diversify during long-term culture our human cell models are used for research for example the study of neurological activity in the case of the iron neurons glute they're also used in disease modeling and 3d printing because bit buyer cells are consistent and scalable they provide a good model for high throughputs screening and a great example of this is our partner charles river who have adopted our ips drive cells into their high throughput screening workflows for use in target discovery validation and screening services and our aim is to democratize access to high quality human cell models and provide researchers across academia and industry with reliable models for research and drug development and so we're working on a wide variety of different cell types so we will be releasing as i mentioned earlier some cell types in the central nervous system space and if you're interested in trying them sooner as a beta tester then please get in touch with us another question is how are you choosing which transcription factors to overexpress yeah sure so that really comes down to the power of our uh of our discovery platform and so that allows us to really do experiments in cells at the bench to screen high numbers and combinations of transcription factors and to determine the ideal transcription factor code that can make the final cell type of interest that we're interested in and this is really powerful and then the data coming out of that is coupled with machine learning methods which will allow us to predict these um in the future um okay another question is um are all the cells you provide diploid the cells that we provide the cells that go into our manufacturing processes are diploid so ips cells are diploid cells um with a normal carrier type we do that's part of our quality controls um that we have at bid bio and um i believe we also check ourselves at the end but we'll need to double check with our with our product specialists okay how many transcription factors can you overexpress at the same time so that's a good question and and it also i guess comes back to how many transcription factors do you really need to make a particular lineage um at the moment with relative ease we can express up to probably five or six transcription factors of course there are lots of ways that we can expand that out and we're looking into that at the moment um you you sort of brought this up earlier but uh another question is how do you qc that you get the right program cells of course yeah so there there's lots of different ways that you can that you can look at and benchmark the cells that you're making um one of the best methods which i showed some data from is single cell rna-seq analysis because that allows you to look not just at a bulk measurement of expression of a particular marker but it really lets you look is every single cell in that population expressing that marker and to the same level and it really gives you high high order information about really what is the transcriptome of each individual cell and how well does that match the cell type that you're trying to model of course the questions of what's the best benchmark is a little bit of a difficult one because even primary cells freshly isolated versus primary cells kept in culture will will display transcriptional differences so that can that can make it a little bit difficult to say uh exactly what um you know what's your what the goal you're trying to hit is but um in general that's a really good way of qc and then once once you know you know classical markers that they should be expressing then they can of course be tested either at the protein level by immunofluorescence staining or at the transcriptional level by quantitative reverse transcription pcr okay um another question do you try to engineer the expression level of the transcription factors or is it more of an overexpression versus not sorry could you repeat that i just missed that one sorry so do you try to engineer the expression level of the transcription factors or is it more just sort of an overexpression versus not expressed so i mean the beauty of the doxycycline inducible system is that it's um it's inherently titratable so if um like all of our products that we're releasing we have established the correct concentration that is required to reach the reprogramming that we need so that's in built into the optics system because of the dox inducible system so we have the ability to vary the expression level um have you ever made direct comparisons between the ips cells produced and versus native cells so did you say versus native cells yes uh i i believe so you don't mean ips sells you mean the um the final um the final reprogrammed cell product and and um yeah i believe that there's been some there was some slides in a recent webinar from our ceo that that looked at ways of comparing um the identity of the cells that we make in a reprogramming versus the mature human cell type that we're trying to model so we have done benchmarking experiments like that i don't have the data in this slide deck though if you're interested again you can get in contact or you can check out that webinar which i think is accessible on our website okay um does your platform alleviate the need for growth factors during the differentiation process yeah that's a really good question um what i would say is that it it certainly allows the simplification of the um of the extrinsic signals so so the media components um however at the moment certainly there is still a need for some extrinsic cues there still needs to be media in which the final cell types are are happy and and performing their functions and so there are still um depending on the cell lineage some um growth factors or various additives in the media but typically they're simpler than the media required for direct differentiation protocols um the question is the optix integrating or non-integrating yes so as i mentioned it uh involves targeted integration into genome safe harbor sites so these are sites in the genome that have been widely used they have the advantages that it's established that they are transcribed in the majority of different human cell lineages and therefore they should remain open no matter which cell type you try to make and ese's targeted integration are at two different genome safe harbor sites for optiox okay another question that comes in have you considered making disease models using these cell lines for neurogenetic neuro neurodegenerative diseases i the question is i do see a need for this in our work at our research foundation and it is very hard to come by good human cell models yeah it definitely this is something that we are pursuing at the moment something that we're looking to expand and if you're interested in a particular model i urge you to get in touch with us and we can start a conversation that is something that i think is a really exciting application of of our cellular models there's a lot that can be done with kind of wild type human cell models that are reproducible and consistent however um it is um it's certainly also very powerful to be able to do disease models with these so something that we are actively exploring at the moment so please get in touch if you're and we can we can discuss what you're interested in exactly what one um okay um uh have you discovered many novel dna sequences that can cause a differentiation in ips cells i'm not quite sure i'm not quite sure what that question is asking in terms of novel dna sequences i mean if if we assume we're talking about novel transcription factor codes um i would say that our discovery platform is um is capable and is we've shown that it's we've demonstrated that it's able to generate new transcription factor codes that that haven't been published before so we are definitely generating and discovering new transcription factor [Music] codes okay um can you comment on the difference between your system and using an episomal plasmid to avoid any genetic changes so and an episomal plasmid um so the the main differences are going to be in the scalability and the homogeneity when you introduce an episomal plasmid you need to transfect the cells which means that inherently that's difficult to scale there are high throughput platforms for that now but they're not widely available or you know even those are somewhat limited in their scale so you you need to transfect the cells then you've got issues where maybe there's transfection efficiency differences so already you might have some cells that don't receive the episomal plasmid and don't therefore don't reprogram or you need to use some sort of drug selection to enrich and then you've also got the issue where you can't easily control the copy number of that that episomal vector and therefore you can lead to differences in the reprogramming outcome both sell to sell in that batch that you've just tried to create and also experiment to experiment because every time you do that transfection it's going to be a slightly different outcome and therefore for you know for some applications maybe that's okay but for things where you really need consistency and purity what you want to have is you know every cell in the dish doing the same thing at the same time and for things like high throughput drug screening this is imperative because if you don't have if you have any extra sources of noise in your system they can destroy your signal and therefore suddenly um you know what was a hit is due to noise or you miss out on hits or on things that could have been hits because um your system is not showing the sort of um signal definition that you need so um really the op dx platform allows for the scalable and reproducible production of large batches of these cells that all do the same thing um as well as the fact that they have the advantages that that they're all the cells are doing the same thing at the same time okay i think we're coming very close to our end so i just want to ask one last question the question is i would be keen on using these cells what do i get in the tube do i get the cell or the cell lines current cells available take weeks to differentiate neurons yeah sure so um our cells that uh we've produced so they will have undergone an induction phase so that they are primed to already reprogram to the lineage that we're making and then they're cryopreserved and so when they're shipped to you these cells rapidly mature and uh and become post-mitotic and they are so the speed to reprogramming and differentiation is much faster for the end user you also never have to know how to culture an ips cell they're ready to use um and really that's another great advantage of all the cells that that you get in that tube okay so i think we're just about out of time and we want to be respectful of everyone's schedule um as a quick reminder after you leave the webinar will be redirected to a brief survey if you have a moment to spare we would really appreciate your feedback thanks again to dr michael d'angelo of bitbio and thanks to all of you for joining us here today we really do appreciate it until next time remember science doesn't stop and neither will we stay safe and have a good day | ↗ |
| 120 | The Butterfly's Whisper Meditations | Biodecoding Meditation: Dialogue with your Cells to Reprogram your Hea... | 125950 | 3102 | 178 | 53.2 | positive | 2:03:57 | No transcript | ↗ |
| 121 | Mayo Clinic | Regenerative Medicine: Making the Impossible Possible | 7653 | 91 | | 53.1 | | 2:30 | The heart muscle cells that Dr. Tim Nelson views highlight recent advances into regenerative medicine. The simplest way to explain that is it's the opposite of degeneration. Tissues in your heart, joints and other areas can degenerate or break down with time or disease. The regeneration is the renewal of those tissues, which is something the body does naturally. So one strategy is to try to find ways to improve the healing of your body. And another strategy is to actually supplement or augment the stem cells in your body so that we can improve the healing by transplanting stem cells into it. Dr. Nelson and his colleague Dr. Andre Terzin used stem cells in their research because stem cells are responsible for growing new tissue. So stem cells just means that they're seeds that can grow into many, many tissues. Stem cells can come from a variety of places, embryos which are not generally used anymore, umbilical cord blood, adult blood or adult bone marrow. So the type of stem cell will dictate how many different types of tissues can emerge out of it. Scientists can engineer stem cells into the type of cells they want. Here's how it works. Cells called fibroblasts are removed from a patient's skin. They're reprogrammed into what are called pluripotent stem cells. Those cells can be taught to become any type of healthy cells, such as these heart muscle cells. The idea is that the newly engineered healthy cells, when introduced to say those of failing heart, will help restore or regenerate the function of the unhealthy cell. This is one cell that's contracting, is working with many cells and that gives the whole tissue the contraction pattern like a normal heart. It becomes much more real when you have a personal connection to a disease or an illness where we don't currently have good options. And this is where people are asking more and more of the questions, what about stem cells? The answer is researchers, such as these at Mayo Clinic, push forward to make regenerative medicine a reality for patients searching for successful treatment and perhaps cures. For Mayo Clinic News Network, I'm Vivian Williams. | ↗ |
| 122 | MESTRO | Immunomodulation and Checkpoint Inhibitors. (Dr. Ikram A. Burney) | 22 | 4 | 1 | 53.1 | positive | 29:22 | No transcript | ↗ |
| 123 | Charles River Labs | Induced Pluripotent Stem Cells: Cellular Shape Shifters | 2458 | 47 | | 53.0 | | 4:19 | Last year, scientists from China effectively cured a 25-year-old woman with type 1 diabetes by reprogramming cells from her own body to their biological beginnings to become nature's ultimate conjurers of creation, stem cells. This first-ever treatment has reignited interest in harnessing these specialized cells, known as induced pluripotent stem cells, to create new generations of cell therapies, not just for type 1 diabetes, but other diseases as well. Induced pluripotent stem cells, or IPSCs, are a little like those science-fiction characters we've seen on etsyphiles or etsymin, who can become whoever, whatever their heart desires. In this case, stem cells can grow and morph into any kind of other cell in the body, be it a liver cell or a heart cell, brain cell or kidney cell. With this limitless potential, they offer hope to treat almost any disease and can be the foundation of ideas from science fiction, like artificial organs and re-growing new limbs. We have known for years how to generate IPSCs using viruses that trigger changes in the genes of adult cells. Unfortunately, when you use this approach, you run the risk of invoking dangerous mutations or cancer, as the line between spawning stem cell and precarious cancer cell can be quite thin. By using complex cocktails of chemical compounds, scientists can avoid viruses and genetic mutations to reprogram adult cells into stem cells, possibly reducing the risk of triggering dangerous side effects in patients. It was only three years ago that scientists discovered the secrets of chemical conversion for human cells, the potion that could transform a human skin cell into a stem cell. Now, we know it can work to treat and perhaps even cure diseases in people, opening the door for new possibilities in stem cell therapy. Not only do IPSC-based therapies have broad implications for the 8.7 million people with type 1 diabetes. Their potential to treat other autoimmune diseases, as well as liver and heart disease, are huge as well. And for the hundreds of thousands of people on organ transplant list worldwide, they could be the building blocks for new organs designed and grown in laboratories. Not surprisingly, more developers are revisiting IPSCs as a strategy for cell therapy development. Analysts estimate that the stem cell therapy market will grow 15% by 2029, fueled primarily by the emergence of IPSCs. Manufacturing these cell therapies can be challenging and complex, and the industry is turning to advances in biology, automation, and even AI to meet this growing demand. Manufacturing IPSCs using a patient's own cells are difficult to commercialize, so companies are seeking workarounds to this process by using donor cells. If we could have one or a few giant banks of IPSCs to meet the demand of tens of thousands of patients, a master source. This could make IPSC-based therapies more affordable and more accessible. Scaling up stem cell production to this level is not easy, especially in accordance with strict government regulations and good manufacturing practices. But the best companies are investing in the mines and the machines to meet the needs of the masses. Today, we can celebrate the potential cure of one patient. Tomorrow it's back to the lab again. Here, scientists and doctors work tirelessly so the few can become the many. So that one day, people may be treated with stem cell therapies like they are treated with antibiotics or other drugs. With the tens of millions of people in need of new cells, new tissues, and new organs, the need is certainly great. But the potential of stem cells? Why that's limitless. Thank you, Sarge, for sharing your expertise. And join us next time for another episode of Eureka's Dose of Science. | ↗ |
| 124 | Keck School of Medicine of USC | Stem cell therapy has potential to extend stroke recovery window | 3301 | 42 | 4 | 52.9 | negative | 0:53 | Could stem cells help us to regain brain function after stroke? To answer this question, we recently transplanted neural stem cells into model of stroke. And what we found was that these grafted cells were beneficial in several ways. They helped the vascular repair, helped with protection of the brain, and reduced inflammation. The grafted cells contributed also to long-term recovery. A second focus of our study was not only to understand the therapeutic effect, but also to understand the interaction between the graft and the host. And we found that our cells turned into very specific neuronal subtypes that communicated with the host tissue through regeneration associated pathways. And you can learn more about this study if you go on kek.usc.edu. | ↗ |
| 125 | The Health Lens | Matcha Magic The Supercharged Tea That Kills Breast Cancer Stem Cells!... | 3 | 1 | | 52.9 | | 2:17 | Well, this is where knowing a little bit about what you're eating is actually useful because Earl Grey is a fermented, it's a black tea. It's got bergamot in it and bergamot is a kind of a citrus. So maybe it's combining those ingredients that actually provides the superpower. But I do see matcha on this tray. I want to tell you about matcha because it is a, matcha is truly a super enriched polyphenol enriched tea. A lot of people don't realize it. There's no tea bag in it, it's no worry. So a lot of people think about matcha as just another green tea, but it's not another green tea. It is made with green tea leaves, the same kind of green tea leaves, but as you would find in any green tea, however, it's what's the composition of matcha. Matcha is green tea that is before it's ready for harvest is grown under a shade that changes its chemical structure, natural chemical structure a little bit. So it's got a lot of potency to it. And what happens with matcha is they take the tea leaf, they take out the stem of the green tea leaf, and they ground up the actual leaf into a powder. Now, what's in that green tea leaf? You've got not just some of the polyphenols that might steep out in the cup, whether you're using a tea bag or loose-sleeve tea, you're getting all the polyphenols suspended in that. So now you get 100% polyphenol, okay, in matcha. So go ahead, you're, go ahead do it. That one's good. All right, okay, for matcha. And because you're getting the tea leaf ground to it, you're also getting your dietary fiber. The dietary fiber is good for your gut health, your microbiome, good for your metabolism, good for lowering inflammation. And the polyphenols found in green tea have also been matcha, matcha tea have also been found in the lab to kill breast cancer stem cells. What's a breast cancer stem cell? What's a stem cell? Cancer stem cell? Well, look, stem cells are these renewable cells. All right, and cancers contain stem cells that help the cancers come back, right? | ↗ |
| 126 | UC San Francisco (UCSF) | Stem Cells for Regenerative Medicine | 38810 | 211 | 8 | 52.8 | neutral | 3:29 | When many people think of cell therapy, so therapy from stem cells, people think about cells which are going to be directly from them turned into safe, for instance, their heart cells or, for instance, their retinal cells or something like that. And that is, in fact, how some of the first trials are going to be done. But, in fact, that's not the kind of cell therapy which is most likely going to happen for large groups of people. It's much more likely, in fact, that people will be able to get cell therapies from stem cells that are essentially off the shelf. So we have banks of cells which have been carefully selected so that there's quality control so that they, for instance, don't have any genes that would cause tumors. And also that they have been selected because they have immune characteristics that make them more likely to be accepted by somebody. It would be very inefficient, for instance, to make 20 or 30,000 embryonic stem cells for which you don't know what the genetic background is or be almost impossible to make IPS cells from all of those people. But because the people are pre-essentially pre-made, they're carrying this condition. They're universe donors. They don't really know it even. And they've given blood or they've given samples to some sort of genetic bank. And then they can be rapidly identified and then contacted and maybe just give a little bit of blood and use that blood to make now IPS cells that can now grow retinal cells, heart cells, brain cells, cells that could be used and these cell banks could be used over and over and over again. Human genetic diversity does play a role in this. So Japan and Shinnyamunaka in his lab in Japan has actually moved forward very quickly on this. And Japan is actually very well suited essentially to pioneer this new technology of these universal donor cell banks because Japan is actually a relatively homogeneous population. It's essentially one island with a hundred or a set of islands with a hundred million people that are relatively homogeneous with respect to their genetic background. And so it's actually estimated that they'll be able to make one bank that could potentially cover 80 or 90 percent of the Japanese population. It's going to be a bigger challenge of course for the rest of the world and for the United States in particular because we're much more genetically diverse. However, if we can learn from what they've learned in Japan and we can do it say for instance more efficiently, there's no reason that we can't have a cell bank that covers a large majority, perhaps 90 percent of our population. It's going to be much more difficult than what they're doing in Japan. | ↗ |
| 127 | Myeloma UK | Immunomodulatory drugs | 9957 | 62 | 4 | 52.7 | positive | 2:33 | Immunomodulatory drugs are really effective for the treatment of myeloma and this is because they work in several different ways to affect myeloma cell growth. So not only can they kill myeloma cells directly but they can also alter blood supply taking nutrients to myeloma cells, they can affect the way myeloma cells stick in the bone marrow and also boost the patient's own immune system to fight myeloma cells. The first immunomodulatory agent that was used is called thylidamide and this is part of a family of drugs which have subsequently been tweaked to make them more effective and have fewer side effects. So there are generations of these called lentalidamide or revlimid and pomolidamide or imnevid and these two drugs are now being increasingly used for treatment in myeloma. The most recently developed immunomodulatory drug pomolidamide shows a lot of promise for patients at relapse and a recent large clinical trial showed that for those patients taking the pomolidamide the myeloma took longer to come back. All of the immunomodulatory agents have the potential to cause birth defects and so patients and their doctors need to have a discussion about how to prevent this. Other side effects with immunomodulatory agents include gastrointestinal disturbances such as constipation or diarrhea and sometimes damage to the nerve supplying sensation to the fingers and toes which is called peripheral neuropathy. Most of these side effects are less with the newer generation of drugs such as lentalidamide and pomolidamide. Immuneemodulatory drugs are particularly effective for the treatment of myeloma because they attack a lot of different pathways in the myeloma cell. They're also relatively easy for patients to take because they're a tablet treatment and don't require the patient to be in hospital. And increasingly they are being shown to be effective at all different points of patient treatment. | ↗ |
| 128 | nature video | Method of the Year 2009: iPS cells | 76247 | 497 | 16 | 52.5 | negative | 5:26 | In 1996, the world's first cloned mammal, Dolly the sheep, was born. Her birth proved that the mammalian genome could travel back in time. Placed into an egg, the DNA of a specialised or differentiated cell gained the powers of an undifferentiated stem cell. Inactive parts of the genome were reawakened and directed the development of a whole new animal. Dolly's birth launched a race not to cloned people but to find a way to make human embryonic stem cells from a specific individual. Embryonic stem cells can make any sort of body tissue so this promised to provide tailor-made human cells for research and transplantation. But making cloned embryonic stem cells in the lab proved very difficult and on top of that, in 2005, the field was bruised by a high-profile fraud. Around this time, Shinha Yamannaka finished his own experiments. He'd found a way to make cells similar to cloned embryonic stem cells but without using eggs or embryos making the process much more straightforward. His technique was so revolutionary he worried other scientists wouldn't believe him. Using just four genes, Yamannaka had changed mature mouse cells into pluripotent stem cells, cells that could then be used to make almost any cell in the body. Yamannaka named his reprogrammed cells, induced pluripotent stem cells or IPS cells. At first, the scientific community was skeptical, but once Yamannaka revealed the identity of the four genes, other scientists quickly reproduced his work. One of these scientists was Conrad Hochheadlinger. He engineered his mouse cells to make green fluorescent protein whenever a crucial stem cell gene was active. Then he tried Yamannaka's reprogramming technique for himself. To his astonishment, his cells glowed green. They had indeed turned into stem cells. Hochheadlinger and other scientists showed that these stem cells were capable of turning into all kinds of tissue in mice, including heart tissue, skin and even sperm. Then came human cells. Just a few months later, more scientists showed that our own cells could also be rewound to a stem cell state. So much for cells in dishes, the ultimate test was to make healthy fertile mice entirely out of IPS cells. Recently, IPS cells rose to this challenge too. Nature methods has named IPS cells Method of the Year 2009 because of their promise as tools to study biology. Although IPS cells were first made some years ago, it's only now that they are beginning to be used in this way. Studying the cellular machinery that enables an IPS cell to turn into another cell type could help us understand what makes a nerve cell acquire the ability to transmit impulses or a heart cell to beat. Researchers are also excited about using IPS cells to study human diseases in human tissue, likely to be a more accurate way to model disease than using mouse models. One of the first studies to use IPS cells to study disease was by Clive Svensson. He made IPS cells from cells taken from a young boy with spinal muscular atrophy and then turned the IPS cells into neurons. This enabled him to study the differences between disease and healthy brain cells. There are still a few problems with this approach, not all cells that look like IPS cells have actually been thoroughly reprogrammed, so researchers are working on better ways to make an assess IPS cells on their offspring. And this work won't spell the end of embryonic stem cell research. Embryonic stem cells are still the best understood pluripotent cells, and it remains to be seen if IPS cells are entirely equivalent to them. But the IPS revolution has most definitely begun. In the last year, labs all over the world have published high profile papers, and many research groups are starting to make disease-specific IPS cell lines. In the next few years, these new additions to the biologists toolkit should start to show their full potential, increasing our understanding of human diseases and the basic workings of our cells. | ↗ |
| 129 | STEMCELL Technologies | How to Reprogram Fibroblasts into Human Induced Pluripotent Stem (iPS)... | 21169 | 228 | 15 | 52.4 | neutral | 5:07 | This video presents an easy and reliable method for reprogramming human fiber blasts into induced play potent stem cells using repro RNA OKSGM. We'll be demonstrating how to use repro teaser, neonatal human dermal fiber blasts and the repro RNA OKSGM non-integrating vector system. The reprogramming protocol can be broken down into three steps, transfection, induction, and selection. The repro RNA OKSGM self-replicating vector only requires a single transfection. For transfection, we recommend using our repro RNA transfection reagent. Simply mix the repro RNA OKSGM vector in a tube with a transfection reagent and incubate for five minutes. Take your previously plated somatic cells on a major gel or vitro net and XF coated plate and replace the somatic cell medium with growth medium containing B18R. Add the repro RNA vector and transfection reagent mix, drop wise onto the cells. Gently rock the plate for even distribution. After one day, begin the selection process with growth medium containing pure micein and B18R. Change the medium daily for six days. At seven days post-transfection, replace the medium with repro teaser containing B18R and continue changing the medium daily for the remainder of the induction phase. Over the next several weeks, IPS cell colonies will begin to form. When reprogramming fibroblasts, the cells will change shape, appearing more rounded as the mesenchymal to epithelial transition occurs. Around day 8-9, small epithelial-like cells will begin to appear. Around day 14-16, these cells will have developed into small clusters of tightly packed pre-IPS cell colonies. And by three to four weeks, large colonies with ES cell-like morphology will be present. In addition to fully reprogrammed IPS cell colonies, differentiated colonies and partially reprogrammed colonies may be present in your cultures. It is important to accurately distinguish between fully and partially reprogrammed IPS cell colonies to ensure successful selection and clonal expansion of the selected clones. Fully reprogrammed IPS cell colonies generated with repro RNA and repro teaser will display the morphological characteristics of embryonic stem cell colonies. That is, they should have distinct borders. Cells should be tightly packed with prominent nucleolite and have a high nuclear to cytoplasmic ratio. To isolate the IPS cell colonies, either a pulled glass pipette or a 22 gauge needle is recommended. Colony isolation should be performed using a microscope in sterile conditions. Sometimes, the colonies you want to select may contain differentiated cells or fibroblast overgrowth. These unwanted cell types should be removed from colonies prior to isolation. Drag the needle or pipette around the IPS cell colony to separate the fibroblasts or other unwanted cells from the undifferentiated IPS cells you are selecting. Use of repro teaser will generate cultures with fewer fibroblasts and differentiated cells, minimizing the need for manual removal of these cell types. To then isolate the selected IPS cell colonies, drag the needle across the colony, up and down, making a grid. Lift and collect the colony fragments with a 200 microliter micro pipette and transfer to a new culture dish. The dish should be pre-coded with matrogel or vitro-neckedin XF and contain M-teaser or teaser E8. IPS cell lines generated in repro teaser and then subcultured in M-teaser or teaser E8 typically contain very low levels of differentiated cells as early as passage 2. And are therefore ready for banking and characterization earlier than IPS cell lines generated with other methods. Successful generation of new IPS cell lines should display normal carry-o type, express undifferentiated cell markers, and differentiate to all 3 germ layers using either in vitro assays or a teratoma assay. For more information about repro RNA, repro teaser, and or other products for pluripotent stem cell research, please visit stem cell.com. | ↗ |
| 130 | RegenOrthoSport | Dr. Movva Explains Regenerative Medicine: A Game-Changer in Healing | 1341 | 28 | | 52.1 | | 0:58 | What is regenerator medicine? Regenerator medicine is basically as we age or an injury. So you start wearing the jaw and you start wearing the cartilage, right? So you're losing, losing and your body is trying to make it. Sometimes it's hard to make it because some of these materials like your cartilage, ligament, tendon, do not have enough blood supply. So what happens, they continue to degenerate. So if we can regenerate that particular, say like the cartilage or tendon or ligament, that is called regeneration. Anything that can regenerate, it tissue that is naturally degenerating is regenerative medicine. We didn't know how to do it, right? But now you have a material. Your own body makes these regenerative material. We are healing with our own stem cells, right? Now the common person, like everybody we can use it because the research started then we have gotten enough data, enough confidence, enough results so that we're able to use it. | ↗ |
| 131 | ScAIence | sort5 The Promise of iPSCs: Modeling Neurological Diseases and Discove... | 15 | 1 | | 52.1 | | 0:47 | It might help treat ALS. Like finding a hidden treasure in your attic. But there must be challenges, right? With IPSE research, it can't be that easy. Of course not. One of the big ones is making sure these IPSE brain cells, they're really high quality and mature. They need to be just like the cells in a real human brain or our models won't be accurate. It's not just about making a neuron, it's about making the right neuron at the right stage of development. Exactly. And it gets trickier with diseases that show up later in life, like Alzheimer's. Right, because those IPSEs, they're like brand new cells again. So how do they, like, how do you make a cell age in a petri dish? Good question. Researchers are working on techniques for that right now they can expose the cells to different kinds of stress or they can change certain genes that are involved in aging. | ↗ |
| 132 | Sydney Children's Hospitals Network | Stem cell therapy - how they work | 19774 | 62 | | 52.0 | | 6:02 | Stem cells are cells in our body that act as the building blocks that may divide and create new cells, maintain or even repair cells, tissues or organs in the body. There are two main categories of stem cells. Pluripotent stem cells are immature cells that can divide and change to give rise to many different cell types in the body. In contrast, adult stem cells are cells which have already fully developed or chosen a role, and these function as maintenance and repair cells. Stem cells make replacements for cells that are lost through wear, tear, injury or disease. These functions are carried out naturally by our own bodies. The latest research shows that we may be able to use some of the same stem cells for therapeutic purposes. Currently, the only stem cell based products that are approved for use in Australia are blood forming stem cells from cord blood or bone marrow. This is called hematopoietic stem cell transplantation. This is a therapeutic option for some children with a select number of rare neurological disorders. Such as metochromatic leukodystrophy, crabe syndrome, hurler syndrome, hunter syndrome and X adrenolucodystrophy. Stem cells are also being researched to develop new therapies in the hope that they may be able to help protect vulnerable brain cells and support their function, while other cells may be able to help repair or promote natural repair. Global trial registries can also help you find out more about specific stem cell clinical trials in Australia, the USA and other countries. As with any medical procedure, there may be risks associated with stem cell therapy, and not all stem cell therapies are the same. So it's important to talk to your doctor about the benefits and risks beforehand. The risks can depend on the types of stem cells being given, how they are given, such as into a vein or directly into the brain or spine, and the drugs that are used to support the therapy. While side effects may not be common, they can be serious and include infection, allergic reactions, blood clots and the rejection of the cells by the immune system. Number formation, although rare, has occasionally been seen with some immature stem cell therapies. With all of this in mind, it's important to note that undergoing an experimental stem cell therapy may interfere with other treatments and disqualify you from participation in other registered clinical trials. As for the benefits of stem cell therapy, they all depend on the exact type of therapy. Clinical benefits may include preventing the condition from worsening and stabilising or improving some symptoms. If you are thinking about stem cell therapy, you may like to use a checklist to help you explore the risks and benefits for your child and talk to your doctors. It's important to ask about the potential clinical benefits and risks of the therapy. The procedure, the ongoing medical care and other considerations such as cost. Remember, always ask your healthcare professional to explain the risks and benefits. When you're in this rare disease space and you're faced with a decision of possibly an experimental treatment and you need to really weigh up risk benefit analysis, but you need to look at what's my child's life like now and what could potentially be like if we do this new treatment. What's important is it's open to weigh communication with your medical team to help you make those decisions. You don't have to make them on your own. We met as a team, we met with the genetics people and they gave us a lot of as best information as they could and that's been developing as we've gone along. Initially, you feel completely isolated and frightened, obviously, but once you are connected with the right people and the right medical team and what not, it does bring a lot of comfort. A motivation to then move forward and find more information and do everything you can and your power to help your child. And so never be afraid to ask questions and I have learnt that as a mum on the journey and, you know, knowledge is power. Your doctors are always here to support and guide you. However, this series of videos is designed to inform you up front as ultimately this is a decision that you must make for your child. As you go through your journey, always remember to ask for support early on. Make the time to take care of yourself. Ask yourself what tools you need to make an informed decision. Stay engaged with your medical team and continue to provide a caring and supportive environment for your child and do your best to not become overwhelmed with information. Instead, focus on what works best for you so you can concentrate on what's most important and what things you want to know more about. More information on STEM Self Therapy can be found on our website. | ↗ |
| 133 | Genentech | Building a Body of Evidence: Translational Medicine | 22387 | 22 | | 51.5 | | 3:09 | Early clinical development is a time that we learn an incredible amount about the drug for the first time in humans. And we have to be very flexible and nimble in changing our strategy as we learn new information. Clinical trial design is really an art. You want to get the right patient population, you want to make sure you're measuring the right endpoints, you want to do the right size of trial, you don't want it to take too long, you don't want to expose more patients to a drug that maybe doesn't work than you need to determine that. And so how you conduct clinical trials is extremely important in being able to develop drug successfully. In our early clinical trials, at each one of the phases, whether it be preclinical, whether it be phase one or it be phase two, what we're ultimately trying to do is build a body of evidence. And that body of evidence is safety and tolerability first and foremost for the patient. The second is efficacy. Are we hitting the target that we thought we were going to be hitting with our molecule? Those are things that we're thinking about in phase one. Then we take those into phase two where we're testing multiple doses, but we're actually looking at proof of concept. And proof of concept means we're actually having a clinical response. One of the most important parts about science is to be objective. To look at the hypothesis that you've formed, understand how you are going to test that. And in clinical trials, that's a little more complicated, you can't control all the variables. But if you can get the right questions in there, then you can really start to put together a coherent story. And it'll either tell you that you're able to help people or it might tell you this didn't do it. But we have a good idea about what's trying next. We have, among our early clinical development group, many of us continue to see patients on a regular basis. And I think that allows us to do our job better. It helps us to understand what clinicians are really looking for in terms of new therapeutics in all of the disease areas that we work. It helps us understand what patients want and expect from a new drug. From a patient perspective, we try to really understand how it feels to have the disease. And think about disease modification, not just in treating the patient's symptoms from the disease, but also affecting their whole quality of life. This is the largest biomarker intervention I've studied at me. If we can understand the science which we have been trying to do very carefully, and we can apply that to medicines that work in these patients, it will be life changing for these patients and their families. And for me, that's what gets me out of bed in the morning, the potential of really having an impact. | ↗ |
| 134 | AAAS_org | Science Translational Medicine | 11316 | 40 | 2 | 51.3 | positive | 5:54 | Well, we need to continue our efforts at basic research to uncover new and fundamental knowledge. It's important to also focus on how this knowledge can improve human health in real terms. Often it's at the interface of disciplines that combine multiple fields of knowledge, the translation of the deeper scientific insights that come from the lab can find their beneficial expression in patients. That's what translational medicine is about. The most efficient way to understand all streams of knowledge and create new knowledge with it that has a direct impact on public health. There are engineers that devise new medical devices. There are biochemists that devise new chemical agents that can be used as drugs. There are computational biologists that devise algorithms that can improve imaging methods. All of these things are part of medicine, but they're from widely divergent groups with different expertise. The mission of the journal is to try to stimulate more effective science in this area by bringing the bare powerful voice for innovation. This journal, Science Translational Medicine, really truly reflects the need of the scientific community to focus on what we call the field of translational medicine. Why is that? It's become very obvious that over the past 10 years we've made an enormous amount of progress and discoveries at the basic level. But as we've done so, we've realized that biology is much more complex than we thought it was. And this daunting complexity makes it quite difficult to take that knowledge and translate it for human health for human patients. So this translation used to be quite linear in the past. You could do it quite straightforwardly, not anymore. You're doing it now, in part, because of the increased interest in translational medicine that we see coming from organizations like the National Institutes of Health, but from patient groups, from basic scientists who want their work to get translated into clinical practice. They need an outlet. They need a place to talk about this important interface between basic and clinical research. Innovation happens when you bring different ideas and different approaches together in new ways. And so this journal is a meeting place for those different ideas. And it will try to encourage in its reviews and in its editorials new ways of thinking about important problems. So this journal will be centered around original research papers that make significant contributions to translating basic science results into improvements in clinical medicine. Which we're also going to be having commentary from experts in many areas that touch on translational medicine, the regulatory environment, from pharmaceutical industry, from patent law, from people interested in legislation. That doesn't exist today. That's what this journal is going to do. So if you think about it, this is a sort of multi-directional process where basic research informs clinical research, clinical research informs basic research by posing critical questions that need to be answered. We want the journal to address problems that a broad group of scientists and physician scientists are interested in. We want to appeal to engineers. We want to appeal to clinical physicians. We want to appeal to chemists, basic scientists, people in pharmaceutical industries. Triple AS has published science for a long time and we do have another knowledge environment called science signaling. The whole of the hair at Triple AS is very excited about it. The partnership between translational medicine and Triple AS makes perfect sense. Why? As I said, you cannot make progress in translational medicine unless you understand. A, the complexity of the underlying science and B, the fact that it requires the collaboration of multiple disciplines and it requires people are willing to go out of their silos, one of the comfort zone and break the barriers that sort of constrain them to their very narrow point of view. Well, what organization really does that well? Triple AS. We expect this to be a tremendously important contribution to science because we'll provide a forum, we'll provide a venue where basic and clinical researchers can talk to each other. | ↗ |
| 135 | SABC News | Discussion | Stem Cell Reprogramming with Dimakatso Gumede | 780 | 17 | | 51.1 | | 6:45 | is women's month. So let's celebrate some unbelievable women. Now only a handful of people in South Africa have mastered stem cell reprogramming and even fewer women in this field. My next guest is one of them. 34-year-old Dimarchate Gumeire has studied the role of gene mutation that causes skin and lung fibrosis using a scientific method called induced pluripotent stem cells. She currently works at the Council for Scientific and Industrial Research as a CSIR and is here in studio with us. It is so good to see you and welcome to Morning Life. Thank you so much for having me. Congratulations on the work that you're doing but I have to confess upfront I have no idea what it's all about. It's not my fault. It is not my fault. Talk to me. What does it all mean? Our bluripotent stem cells are actually cells that can become any cell type in the body and mainly they've been known to form a human being or any animal which are embryonic stem cells but their scientists have actually made breakthroughs in creating induced bribotent stem cells from adult cells. So you can take a skin cell and turn it back into an embryonic like cell that can become any cell type in the body. It's quite incredible actually and I mean this this form of technology, this form of stem cell reprogramming is massive and I think this is a glimpse into can I say into the future where is it already happening in a big way now? It's happening in a big way but still also in phases where we are trying to make sure that anything that we do does an effect human beings in the long run they are no adverse side effects as we go on with it with the research. So before we get a little bit more technical about it I mean what attracted you to this? Tell us a little bit more about yourself. I'm a UCT student, PhD scholar currently waiting for my results. This is PhD results to come through but it attracted me because of my supervisor that it was Professor Bunganima Yosey and he's been working on families, South African families that have a regenerative disorder but that regenerative disorder is multi-fectoral that it affects the lungs and affects the skin and affects the muscle. So the whole technology of stem cells is that we can make stem cells to any cell that we want to study and if we want to study lung fibrosis for example that we can turn those cells into lung cells, L we can tend them into skin cells or even muscle cells so that's what attracted me to it. That is I mean it's incredible this is it's phenomenal work and that's actually the that was the basis of your thesis as well. You say you're waiting for your results to come through our world. Good luck for that I hope it goes well. But I mean this is something very important. I mean can you can you give us a little bit more? I mean how does that change the way we are and operate and how things are studied going forward? What we're doing actually is to create cellular models to study specific diseases. For example in our lab at the CSIR we are using stem cells to make liver cells to study how adverse drug reactions are happening in the African population because they have such a diverse genetic variation. So that helps us to look at the drugs or study different kinds of drugs and see which ones cause liver toxicity in African individuals and that we can actually recommend or propose that recommended doses which will help those individuals and also assist us while into which drugs to avoid for people who have those variations that have them to not respond well to the different drugs. Now I think what is so great I mean you I'm conducting this interview in English I think I understand English quite well but anybody who doesn't understand English I mean this must be listening to your worst nightmare come true but the most amazing thing with you is that you communicating in Isisulu, Isisulu and I think those are the two languages. Yeah I'm going to language it's a story. And that is incredible because to try and take all of that and make it more understandable for the large community is huge how are you going about doing that? That I have to say that it helps to do Sissoto in as a first language in high school because we know that due to our history you know most of the schools still have English as a first language you know and I think it's a really a good idea to have students and have people learn the native languages in that way they will help to communicate even to their grandparents and their parents about science because really we have to communicate science to every South African in order to understand what we're doing as scientists and medical practitioners. It is so important that I'm so glad that you're doing that because I mean it really as I said up front even for me listening to this in English is kind of as I said you know this is difficult for me to understand but imagine not even speaking English and having to try and understand that and so I am so so glad you're doing this but in terms of of black females in this profession are there many are you breaking down walls and and sort of creating opportunities where they were none before? We have to there haven't been a lot of women getting into science and because science have been mystified in such a way that you know it's too hard mathematics is not easy to understand physics and biology are not easy to understand but it's time to break down all those demystifying the science itself and I'm hoping that there are women who are getting there and I was very fortunate to be mentored by females as well who encouraged me to say you can do it you know if you put your mind into it you can do it and you can learn it you can understand and they made it so exciting and so fun to learn and enjoy and some here that is amazing we are so proud of you and you just keep on doing whatever you're doing and breaking down barriers and shattering glass ceilings and all of those predictive terms that we all use during this month but we genuinely mean it and you're shining like for us thank you for coming to talk thank you very much so nice um democratic remit she's only a handful of people in South Africa and I think I might be as bold as to say on the continent actually not necessarily just in in South Africa who have mastered stem cell reprogramming all right we're going to take a break here on the program sports news after let's do stay tuned | ↗ |
| 136 | University of California Television (UCTV) | Cellular Reprogramming Approaches for Heart Disease - Deepak Srivistav... | 546 | 13 | | 50.9 | | 14:34 | It's a pleasure to speak at the 2020 SIRM grantee meeting and I should say before I start that all of the work that I'll present to you today was funded by SIRM over the last many years and would not have advanced to the point that I'll show you in the absence of that funding. And both stories rely on a cellular reprogramming approach to address human forms of heart disease. And in both cases we've leveraged cardiac developmental networks to either regenerate damaged hearts by reprogramming resident cardiac fibroblasts to cardiac myosite like cells or to understand mechanisms of disease using human IPS cells and then followed by a drug discovery. In the first story we have leveraged the fact that the human heart is made up a half of actually cardiac fibroblasts and less than half of myocytes. And the cardiac fibroblasts are the ones that support cardiac muscle cells but also the ones that are activated to form scar tissue as you see in this section of this heart here. And because the human heart and mammalian heart in general has very little if any capacity to regenerate, once cells are lost after damage as you see here there's no capacity to regenerate. And so we over the years attempted to reprogram these resident cardiac fibroblasts into new cardiomyocytes right where they are in an effort to regenerate damaged hearts. And to make a long story short over the years we were able to find that the combination of these three key developmental transcription factors, Gata4, TbX5 and MF2C were sufficient to reprogram cardiac fibroblast into cardiomyocytes like cells that we called induced cardiomyocytes or ICMs. And this was relatively inefficient in vitro on plastic but could be done. But in vivo in mice we found that this was quite efficient and these resulting cells are most similar to adult ventricular heart cells. They could electrically couple with one another which was key for improving cardiac output. And in fact when measured by MRI these mice did in fact have a significantly improved cardiac function. This is an example of what those hearts look like after coronary ligation followed by gene therapy mediated delivery of these three transcription factors. Following three months later you one can sacrifice the hearts and if you look at the apex cross section around this level you see abundant scar on the control less so at the further up in the heart. And in comparison mice treated with this gene therapy approach had abundant muscle even at the apex as you can see here and we have fluorescently labeled with the CRE based system the fibroblast and can see that all of these are actually newly formed cardiomyocytes. We of course asked will the same combination work in in human cardiac fibroblast and it turns out that in human cardiac fibroblast replacing Gata4 with myocardin, a transcriptional co-activator, 4MF2C actually was sufficient now to reprogram human cardiac fibroblast into cardiomyocytes like cells and you see an example of a beautifully reprogram cell here with these sarcomeres indicated without cardiac alpha actin and so this combination we then tested in vivo in pigs to see if they which is as a heart more similar to the size of humans where an in vitro this combination also reprogram pig cardiac fibroblast. And using an AAV now a vector to deliver these three factors we injected these into pig hearts after a coronary occlusion and co-injected them with a retrovirus expressing DS-RED because a retrovirus will only infect dividing cells and myocytes don't divide so it would allow us to mark the non-myocytes that were infected by virus sometimes co-infected with the AAV and then we can ask whether there are DS-RED positive cells that now have sarcomeres suggesting that these might be newly born cardiomyocytes and you can see here in this high magnification section that there are a number of cells with beautiful sarcomeres that are also red suggesting that these may be newly reprogrammed cardiomyocytes and you can see that a little bit more easily here with the just a DS-RED channel in white and so you can see that this is a fairly efficient reprogramming event in vivo and this was very encouraging that we might be able to generate enough cardiomyocytes to actually make a difference and this is in the border zone of the damaged area and so with this information I'll all supported by SIRM particularly pig translational studies we have put this technology into a startup company called TNIOTherputics that was launched with the 50 million series A financing with the column group and 2016 followed by a series B event last year and they are advancing this towards clinical trials and over the years they have refined the technology and the genetic material that would be delivered as well as a vector and I'll just show you one slide from TNIOTherputics with their approval that shows you a cohort of pigs around 10 pigs either treated with the gene therapy AV or control and in blue you can see that there's a marked improvement in the ejection fraction of these pigs compared to the controls in gray and this degree of improvement of 11% absolute ejection fraction improvement is really quite significant and would be clinically meaningful particularly for those who might be waiting for on a on a transplant list to potentially be able to avoid a need for a transplanted heart and so we're very excited about the TNIOT pushing this forward and we continue to collaborate with them to advance this technology now in the second story I want to share with you as I mentioned it's really one about understanding disease mechanism and doing drug discovery with IPS cells and this story relates to a family shown here where this multi-generation family had a very common form of heart disease called calcification of the erotic valve that you look something like this where the erotic valve becomes hard and calcified requiring replacement surgically and about 100,000 replacements are done a year just in the United States so it's very common disease the etiology hasn't been known and there's currently no medical therapy we do know that about in cases where people are born with a congenital anomaly where there are only two leaflets instead of three in the erotic valve like you see here that's something we call a bicuspid erotic valve that about a third of those individuals will develop calcification as they age into their third fourth fifth to sixth decades of life and this congenital anomaly is actually the most congenital anomaly of all it affects one to two percent of the population it turns out this family had both bicuspid erotic valve and calcification as they got older and it's caused by a heterozygous mutation loss of function mutation in the very well studied transcription factor notch one and so having identified the genetic cause of this we were able to use isogenic CRISPR gene-edited gene corrected IPS cells from this family to deeply understand the mechanism and it turns out that what we found is that normally notch one which sits on the cell membrane is in a position to sense shear stress and its job is to normally repress osteogenic pathways in the endothelial lining of the valve and we know that the endothelial cells of the valve can transdifferentiate and become mizankamo cells and go to the valve and and there that's where this notch is playing a role in preventing this osteogenic fate so essentially the what we found is that in the setting of haploean sufficiency what happens is as endothelial cells undergo more EMT and become more osteogenic so it's essentially a cellular reprogramming event from an endothelial cell to a more osteogenic like cell and this we were able to discover through a deep interrogation of these IPS-drived endothelial cells as shown here that resulted in a deep understanding of the gene network that gets dysregulated and it turns out that the network narrows down to three key transcription factors, SOC-7, TCF-4 and SMAD-1 that are central players that then dysregulate a host of other genes that results in this so-fate switch if you will. And so that gave us the thought that maybe we could drug this process and so we screened a library of 1600 highly curated compounds and instead of looking for one, two, or three outputs, we screened for 120 genes in the network that were dysregulated with each molecule and we used a machine learning approach to classify cells as either normal or abnormal and asked what drugs might reclassify abnormal cells and from this we found six hits that actually had resulted in this change in classification. I'm just showing you here how what this output looks like in blue, these blue dots are wild type cells, normal cells, green dots are what the machine learning algorithm calcified as heterozygous cells and in red are what the algorithm classified as either normal or abnormal. Here you can see that most of the drugs do nothing, they still cluster with the green and so are still heterozygous. However, you'll see that there are a few red dots that are now clustering with the blue dots and these are what our hits are suggest of a drug that is shifting this profile broadly. And so we have taken these six hits and tested them in vivo in a mouse model we generated where the by shortening the telomeres and notch one heterozygous mights to be more like human telomere length, we can actually recapitulate the human phenotype of a calcified and obstructed erotic valve. And so I'm showing you here by echocardiography in these mice, the erotic valve peak velocity which reflects the erotic valve stenosis very similar as occurs to in humans. This is partially penetrant but you see in the control a number of these mice have acceleration of the blood flow across the valve indicative of stenosis both of the erotic valve and pulmonary valve. And one of the six drugs shown here had a remarkably remarkable effect in completely preventing in a statistically significant way erotic valves stenosis in the vast majority of mice as you can see here as well as preventing pulmonary valves stenosis. And by histology these drugs, this drug also prevented thickening of the erotic valve and calcification of the erotic valve. So we think we've got a drug that we discovered in human IPSLs that works in IPSLs to change alter the dysregulation and works in vivo. Now finally we asked would this drug also affect those who don't have notch one mutations as it caused. And to do this we collected, we worked with the group in Russia who had collected primary erotic valve endothelial cells from explanted human erotic valve samples either with three leaflet calcification or two leaflet calcification. And we exposed all these endothelial cells to the drug and then did RNA sequencing. And I'm just showing you here the most important result of the most important factors these three sort of master transcription factors that we know are causing the broad gene dysregulation. And in each case the this drug restored the corrected the upregulation scene in the disease valves endothelial cells to normal whether we're looking at SOC7, TCF4, or SMED1. And it didn't matter whether they're tricuspid or by cuspid of your valves. We saw the same things in the abnormal cells and those were corrected by the drug. And so we're very excited that through this approach we actually have a potential drug candidate which should be the first that works in mice and works in broader populations of human erotic valve cells. And we're considering now how to advance this towards a clinical trial. So with that I'll close and thank the members of my laboratory that contributed to this work including former lab members and our collaborators and of course our important funding from SIRM. And with that I'll be happy to take questions at the end of this session. Thank you very much. | ↗ |
| 137 | National Stem Cell Therapy | What are Induced Pluripotent Stem Cells? #stemcells | 3506 | 68 | 2 | 50.7 | negative | 0:31 | Imagine if we could turn back time on our cells, well we can, meet induced pluripotent stem cells, or IPSCS. Scientists can take regular adult cells like skin cells and reprogram them back into stem cells. That means they can become any cell in the body, brain, heart, even muscle. IPSCs are changing medicine, helping us study diseases, test new drugs, and maybe even grow new organs one day. Pretty amazing, right? | ↗ |
| 138 | Johns Hopkins Institute for NanoBioTechnology | What is Regenerative Medicine? | 1306 | 23 | | 50.7 | | 5:29 | The regenerative medicine is an exciting new field with the potential for providing better lives for millions of people. From cut nerves to damaged hearts, regenerative medicine may have the answers to restoring victims of disease and accidents to their once healthy state. But what is it exactly? Renovarison is a scientific field that aims at developing new approaches and tools to promote tissue regeneration and also trying to understand basic principles and mechanisms. So it is very important for the regenerative medicine field to understand what are the basic set of cues, including environmental cues, biological cues, and cellular cues in the particular tissue environment that stimulates tissue growth. Here at the Institute for Nanobio technology at Johns Hopkins University, researchers are working to provide these answers to a number of clinical applications. So one approach to tissue engineering is re-engineering and repairing damage to the central or peripheral nervous system. And the idea here is again to recreate chemical signals, biological signals that nerve cells brought the broad class of nerve cells that are necessary to repair would be able to have the same types of chemical interactions with the native environment to a scaffold that will present the same kind of chemistry. This often involves a very complex molecular and polymer engineering approach to very chemistry, to very porosity, to very mechanical properties in a way that cells then think they are interacting with a native substrate or native surface that would be necessary to encourage the regrowth of new neural cells or establishing reconnections among these cells. So it is known that certain cells, particularly neurons, are sensitive to electrical stimuli, and their ability to regenerate can be influenced by the presence of an electric field. However, electrical conductors are typically made of metals and other kinds of inorganic complexes. So this is an issue since cells will see these materials as foreign objects and therefore won't like to adhere to them. So using the chemistry that we can present on these materials in terms of interfacing with cells, we then create the artificial function by way of incorporating the electronic or the optical materials. And then these then are carried into the final overall scaffold material. Regenerative medicine is not limited to damage to the nervous system. Another group at the Hopkins Medical Campus utilizes a different approach to treat cardiovascular disease. Stem cell therapy or using stem cells to stimulate and direct tissue growth is a major focus of regenerative medicine. However, they don't tend to survive very well if you just directly inject them into the body. So we have to find a way to protect these cells. And we begin by exploring cell encapsulation techniques for cardiovascular disease. And one type of treatment involves delivering stem cells that will stimulate the regrowth of blood vessels in that area of the heart. So in our group using a technology known as microfluidics, we've developed a platform that can trap only a few cells into these very small and uniform bubbles, about 50 microns in size, that will allow us to deliver the cells directly to the heart muscle. I mean the most exciting thing is we see that the cells in culture, they seem to be very happy when they're just one or two cells in these capsules. So it looks like we may have a much more effective therapy potentially if we can actually produce these in high groupode. For many of the scientists here at Johns Hopkins, institutions like the INBT are not only useful, but instrumental to providing answers to these medical problems. I think by nature research has to be interdisciplinary and at least in medicine. I don't think that any one group really has a broad enough breadth of knowledge in order to really solve these problems. So all of this will require the collaboration among scientists, engineers and clinicians. And in many cases, even a marketing perspective, if one wants to think about eventually translate and this to apply this to a clinical setting to benefit patients, a population population, someone has to make this into a product. So with such a complex task, it is very helpful to have institutions like INBT to put different resources together. Not only just from the training perspective, from a scientific team-managing perspective, but at least get people with different set of agenda or expertise and different set of thinking to come together to solve a common problem. That is the only approach that I personally view will make it successful. | ↗ |
| 139 | RPA Health | Immune Health With Dr. Joshua Bletzinger DC, Part 4: Immunomodulation | 53 | 2 | | 50.4 | | 3:01 | All right, wrapping up our video series with video number four on our immune health system. That's working extremely well for our patients and the people that are close to us in our community and that are following these guidelines from a natural perspective to support their immune system and to support their health. The last one, Immunal Modulation. We want an immune system that can balance itself and we want an immune system that's working correctly, which means that we need an immune system that works from a stimulatory situation into an adaptive or modulated position. And let me give you a little bit of an indication on what that means. First and foremost, when our immune system gets the tracking of a foreign invader, so a pathogen or an antigen, it's going to be met by the immune system and it's going to be met by many aspects of the immune system, which is a stimulatory response. Send everything to this pathogen to see what it is, so we can start to form the right type of response. So that stimulatory, once we figure out what it is, moves to this modulator to this adaptogenic immune response, which is like, okay, we know what this is. We know what we need to formulate in order to thwart the threat of this and and destroy it and get it out of our body. That's the modulation. That's the adaptation. What happens is that if we stay in the stimulatory response, we're overthrowing the inflammatory reactions and we stay there, which means that now we have an unbalanced immune system, a very aggressive immune system, and an overproduction of inflammatory responses and we can't shut it down, okay? So this portion of it once everything else is working right, we've got number one, we've got decreasing the acquisition, we have reducing the replication, we have body systems support, all these foundations will improve the way that the immune system responds to anything that comes into its body. And if we can have a modulated immune system, we have a well-working functional body. And that's exactly what we want to produce. And this happens through lifestyle, it happens through nutrition, it happens through proper supplementation and it happens through exercise. And so we want to continue to give you more information on how this works, but this is just kind of like the the present that's underneath the wrapping paper when you do all this right, that you get this absolute innate response that's supposed to be working right. So if we can help you in any shape or form with your immune system function, with your body function, with a process that's going to help you through these trying times, DM us, comment on this, get on the books for a 15 minute call, we're happy to talk with you, and keep you moving through this time, and we'll all get out on the other side very, very well. So it was great talking to you, and let us know if you knew anything, we'll talk to you soon. | ↗ |
| 140 | TEDx Talks | What you need to know about stem cell therapy | Ernst von Schwarz, MD ... | 125563 | 2661 | 319 | 50.3 | positive | 18:08 | No transcript | ↗ |
| 141 | HealthTree Foundation for Multiple Myeloma | What are immunomodulatory drugs (IMiDs) and how do they work? #myeloma | 4017 | 29 | 1 | 50.3 | | 2:53 | What are immunomodulatory drugs and how do they work? So, imids, of course, have a slightly controversial history prior to the discovery that they were effective in myeloma. Felidomide was, as a lot of people know, initially used for morning sickness in pregnant women. Obviously, that had terrible, teratogenic or birth defect effects. It was later actually realized that this compound could have a beneficial effect in myeloma and it was tested in that arena and had some efficacy. Felidomide also has some nerve toxicity and causes psalmolins. So its next generation agents, linolytomide and pomolytomide, have less of these neurologic side effects and are very effective and better tolerated as well. As a class of drugs, these drugs target both the myeloma cell and also immune cells. What they do is they actually lead to the degradation of specific proteins. They are called Icarose proteins. Those proteins that are degraded actually affect different processes in the myeloma cells that lead to the death of the myeloma cells. Then in the immune cells, in the immune cells, they actually lead to further activation of immune cells. In that sense, that's why they are called immunomodulatory drugs because they have this multiple immune effects where they lead to activation of natural killer cells and T-cells that are thought to be important in part of the efficacy of these drugs. So one form of immunotherapy that probably everybody is familiar with in very broad terms are drugs such as rebel mid and pomolytomide. These are developed as what are called immunomodulatory derivatives of a drug known as poliomide, which was a very old drug. What it does is that it globally improves the patient's immune system in addition to fighting the myeloma. So it probably has several roles. And that has really served as a baseline for a lot of other therapies that have been developed. The large part because it can't continue to modulate and potentially enhance immune responses. | ↗ |
| 142 | VSI® | Spine Solutions | PRP Injections vs. Stem Cell Therapy I Understanding Regenerative Medi... | 2791 | 37 | 4 | 50.3 | negative | 4:33 | One of the common questions I get for my patients is when I'm treating a patient with a spine or an orthopedic condition, when do I use platelet-rich plasma or PRP or when do I use stem cell or bone marrow aspect and so when I talk to them, I really break it down by using an analogy. And so, which I don't know medicine is like growing a lawn or a garden. And when you're going a lawn or a garden, you need soil, you need water, you need fertilizer and you need seeds. These are things that you need. The body needs exact same things. And so, when we're treating an orthopedic condition and we're using regenerative medicine, this is the idea of giving the body what it needs to heal its joints, its ligaments, or its tendons. And so, we do regenerative medicine with two different types of treatments. We do something called platelet-rich plasma or PRP and then we also use stem cell or bone marrow aspect concentrate. That's what we do things that we use. And so, let's break it down. Let's start with PRP platelet-rich plasma. And so, we'll go back to the analogy. The analogy of growing the lawn. So, we said that in a lawn, what you need is you need seeds, you need fertilizer, you need soil, you need water. Well, let's say we have a lawn, but it's kind of scant. It's not growing very well, but you definitely see some grass. And so, in those situations, we may be able to get away with just putting some fertilizer down, just giving it a little bit of a boost to start growing. And so, that's the same thing as putting PRP or platelet-rich plasma in an area of injury. And so, it's the exact same. It's boosting the body's own regenerative abilities to treat an area of injury. And so, the question I always guess, where do you get that PRP from? Well, we get it from the patient's own blood. So, what we do is we just do a regular blood draw, just like you do in a lab corps. And then we process that. We get the fertilizer or the platelets out of it. And then we put it to the area of injury. And so, we boost the growth of the area of injury and just like fertilizing the lawn. But let's say the lawn is terrible. We just don't have any grass, and we need something that's a little more powerful. Well, then we may have to recede the area. So, seeds are the same thing as stem cells, same exact idea. And so, in those situations, when we're really, really bad off, sometimes what we need to do is we need to put stem cells in the area, or seeds in the area. And remember, these are not embryonic stem cells. I get the question all the time. Well, you know, what about the risks of this? Well, we're not doing embryonic stem cells. We're using something called adult mesenchymal stem cells. These are stem cells that can only convert into your own type of tissue. So, there's no risk of cancer or any other things growing. These are just going to grow in the tissue that you want it to grow. And so, where do we get those stem cells from? We actually get it from your own bone marrow. So, what we do is we do a small little bone marrow harvest from the hip bone. And once we get that bone marrow, we divide it, we set a few of it, we get the stem cells out of it, and then we put it back into the area of injury. And so, these options are extremely easy to do. It's a quick recovery. It's very natural. And it's not changing your body. You're just feeling the problem. You know, many times, this is a very simplistic approach to it, right? PRP or bone marrow, but a lot of times what we need to do is we need to do a combination of it. But sometimes we'll start off with an area that's really, really bad, and we'll do a stem cell procedure. And then we have you come back four weeks later, and then fertilize the area with PRP. Or we do a combination. Sometimes we do a PRP a couple of times beforehand, and then do stem cell. So, you really have to take an individualized approach to treating these problems. It's usually not just a one and done situation. We usually approach it and come up with a protocol for each and every patient. But these are, these are different regenerative medicine options that we have to treat orthopedic and spine conditions. So, basically, in conclusion, when we think about what we're trying to do to treat an area, and we're deciding PRP versus stem cell, think of PRP as the fertilizer and stem cells as the seeds. | ↗ |
| 143 | TEDx Talks | The Beauty Of Pluripotent Stem Cells | Muhammad Khan | TEDxBrentwoodCo... | 8204 | 107 | 4 | 50.2 | negative | 6:46 | What if I were to tell you that in the not too distant future, will it reach the point where things like cancer, diseases like cancer will be viewed as something whilst being really horrible or preventable? Now, I actually think that this is not too far away. Sorry, I think that we are actually not too far away from this. Stem cells have actually been used recently in curing some specific types of cancer, for example, leukemia. leukemia is a cancer of the bone marrow. Now, inside the bone marrow, you'll find there are stem cells. These stem cells can become into very specific other types of cells, for example red blood cells. And if someone has leukemia, those cells become cancers. And one way that we actually prevent this is by doing something called a bone marrow transplant. Now, when that happens, the stem cells inside of the bone marrow will then start producing healthy cells that can then kill off the cancer cells. Now, that is just one example of cells that are being used to ameliorate some forms of cancer. But I'm talking about something much larger. Now, before I can really get into this, we really need to understand what stem cells are. Now, at some point in time, we were all a small ball of cells that then decided to specialize into, for example, heart cells, into cells that went into our lungs, into skin cells that then made us who we are today. We consider stem cells to be the building blocks of life. Now, since then, we've realized that we could harness these powers of stem cells. And what scientists discovered was, within the first four to five days of embryo development, we could take the embryo out and use those stem cells into creating fully functional cells that we can then use in regenerative medicine. Until one day, Shinnyaya Manaka came along. And I'm going to tell you a little bit about him. He was an orthopedic surgeon. And what he found was a lot of the time people would come to him, and they would have spinal cord injuries, and there was nothing he could do for them. If someone came in with a spinal cord injury, he would look at them and think, you know, I want to do everything I possibly could. But there isn't much. And with because of this strong controversy behind embryonic stem cells, he couldn't really bring the research that he needed. And it's something that frustrates me so much. And like it frustrates me, Shinnyaya Manaka was frustrated. And what he thought was, okay, well, what if I made my own stem cells? What if I could take something, like, for example, skin cells, and then force them into doing what I want into becoming stem cells? He called those induced pluripotent stem cells. He then dedicated the next 10 years of his life into researching this. And what he found was absolutely amazing. After the 10 years, he found four factors that, when he injected into the skin cells of a rat, like the rat's skin cells think that they were stem cells, and they would start when they were dividing, they would become more and more like these stem cells. At the moment, skin cells are unipotent. We're always growing skin cells, right, to make sure that we have a strong layer of skin on us always. But what Yamannaka did was he took that, something that could only become a skin cell, and he made it into something that could very well become any type of cell. And as a matter of fact, it is because of Chinya Yamannaka's research that I think that we have unlocked a strong potential, and we've gotten over that controversial boundary that embryonic stem cells have brought forward with their ideas of sort of, with the whole fact that because their embryos, it's unethical to use them. And what I want to move on is, because of these induced pluripotent stem cells, we can now start creating cells without that sort of controversy, without the sort of need to have to worry about research funding and things like that. And so people have actually pushed forward with this. And in one specific lab in Tokyo, they, what they did was they went and took induced pluripotent stem cells from rats, from rat skins, and they turned it into human liver cells, or liver cells that could be used for medical purposes. They actually managed to make not a fully functioning liver, but parts of a liver that were fully functioning, but it wasn't actually the whole liver. And so what they did was they put that into the rat, into various parts of rat, and amazingly enough, a vascular system grew around the liver, and the liver integrated itself very well into the rat, and it was actually fully functioning. But why would this matter to us at all, if we can somehow put livers into rats? I don't, like, obviously that doesn't apply to us right now, because there are rats and we're humans, it might not be the same. And whilst that is true, they foresee that in the next 10 years, this might become commercially available. And that is why I think that this is such an important science, because I mean, a lot of you guys probably around six, seven minutes ago didn't even know what stem cells were. And that, to me, was absolutely tragic. Because of Shinnyamunaka's work, I think that we should be much more aware of these cells. And I think that we should actually start thinking about integrating into medicine, which whilst we are, I really see that coming within our lifetime. And that is why I think it's something that everyone in this room really needed to know about. Thank you. Thank you. | ↗ |
| 144 | Mahidol World | Translational Medicine, Faculty of Medicine Ramathibodi Hospital | MU ... | 2466 | 30 | | 50.2 | | 5:02 | We are the first program in Thailand that offers translational medicine as a PhD in master degree courses. In my dream is to be a doctor who is able to understand research is more. The University of Thailand is a very important place for us. Our activity hospital is one of the main hospitals in the U.S. We do have lots of patients coming every day. I think we are in a very good setting that there are very good collaborations between clinicians who see patients and also researchers behind the scenes. The aim of this faculty is that we want to translate whatever it is in bench work or in the lab into the patients. Translational medicine means the integration of knowledge in basic science and clinical medicine to improve diagnostic, treatment and prevention of human health. Awesome please say from bench to bedside. This program provides basic molecular medicine foundation in the first year, including basic mechanisms of diseases, tools and technologies in molecular medicine and biostatistical analysis. After the coursework, students will get an opportunity to do rotation at the OPD and the lab to learn the clinical problem with clinicians and get hands-on in the lab with the advisors. We also offer double degree program with NSYSU, which is a leading research university in Taiwan. Students who participate in double degree program will get international experience and doing research in both university and university. And receive degree from myDON and our partner in the university. In the first year, they taught us lectures about diseases, humans have to face, for example, cancers, genetic diseases and many other things including infectious diseases as well. And they taught us the way technology in researching works. For example, the PCR polymerase chain reaction, DNA sequencing or any sequencing, the way we do cell cultures, they help us with the research workflow. They have this lab and OPD rotation where we meet, I would say, real life situation, the patients that come to the OPD with problems that we can generate research questions out of. So what we are trying to do is we are helping to pool all experts from various fields. The student asks, of course, is one of our teams, so we work in a team base. Our program is multidisciplinary program, so we welcome all applicants who graduate from different fields of work. So it's like healthy data. I have so many friends that are from so many different faculties. I have friends from pharmaceuticals, I have friends from faculty of science, and I have friends from medical schools as well. And that makes me think that for the translational medicine, it is really open to that can exchange knowledge and things. That is something that will really benefit you and I can both do research and be a dentist and both give lectures to the dental students. In this program, there is scholarship of a label for international students. I think the chance is also very good in here to get a scholarship. Even though it's also competitive, it's possible. That scholarship support not only my tuition fee, but also the daily allowance and I'm very thankful for that. Trans-sessional medicine is not just important for Thailand. Especially in developing countries in Southeast Asia and elsewhere, it's one of the signs that can help improve the health care of people in that country. And also you can learn how to use the knowledge in the lab to apply innovation. Eventually we just help the cost of health care economy as well. International programs can help answer our needs right now. No need to be hesitated to join our program, just register and then you can be with us and we can help each other. | ↗ |
| 145 | Hope4Cancer Treatment Centers | The 7 Key Principles: ImmunoModulation | 1782 | 25 | | 50.1 | | 12:42 | Hello Dr. Salinas. I'm Dr. Tony. You know, you have a lot of experience that, hopefully cancer, working with patients on a daily basis, seeing them come compromised with their health. And, uh, Chirbouto, uh, having two PhDs, one in agricultural chemicals, and the second one, I'm medicinal chemistry, knowing the impact of chemicals on the body. To that end, let's discuss one of our key principles that hope for cancer, which is the immune modulation. Uh, when we speak about the immune system, we want to look at both, uh, branches of the immune system. And we want to balance the immune system. Not even the immune system that's too active or inactive or, or hypoactive, right? So, uh, let's discuss Chirbouto, um, about the innate immune system, which is the quick acting immune system. And then jump in, Dr. Salinas, talking about the adaptive or more the long term immune system. Well, innate immune systems are really the super heroes of our body. You know, you can think about the flash or the, or Batman or whatever, you know, running to rescue us, whether it's from a pathogen or from anything else. Now, for most diseases, there seems to be like a black and white wall that divides disease and health. And, um, so for example, you know, you get a, a fever, a bacterial infection, uh, you know, there's very clear demarcation between you being sick and not being sick. Um, in the case of cancer and other chronic diseases, that whole thing becomes a bit of a continuum. And the innate immune system, though, is still extremely important there too. Um, innate immune system are the first responders of the body. Whenever they sense an external organism like a pathogen or even a cancer cell, their goal is to respond. But then their goal is to go ahead and activate the adaptive immune system, right? And then they're going to have to do the salinas, which is a little bit more like a, a more targeted or more, um, a smarter reaction, meaning that it's not just, let's attack, you know, it's more against something specific. It's like a log and a key, for example. And it has two branches also. It has the cellular and the humoral part, which is cells and proteins or antibodies. Yeah, we see every day how this immunocompromised patients that have cancer, of course, and maybe have had tough therapies, you know, at home prior to coming, most likely, they're battling with urinary tract infections or infections in the lesions of the tumors that are open. And so if anything, up regulating the immune system to have these infections go away, will enable the God-given immune system to target the cancer as it's supposed to do and not be distracted by trying to control the infection. Yes. That's something important because we've seen that, let's say these table where the area where we have cancer cells there, we see a flow. The white blood cells towards the cancer cells, but as soon as we put bacteria or viruses or parasites on the table, they will kind of leave alone the cancer cells and try to attack these first. So it's very important that we get rid of all those infections also. And in this terrain, right, what decreases the immune status is toxins, negative thoughts, like life of state that are in our food, in our air, in our soil, in our water. And so we need to clean that terrain. This is where all of our principles, the key principles to cancer therapy have synergistic effects. One of the key ones that I would add to your list is nutrition because that is what really helps the body, the immune system, build itself. It needs those key components that we're eating every day to keep itself in that healthy state. Given the body, the resource is in needs to heal, right? And let's talk a little bit about specific therapies that we have at Hope for Cancer that upregulate the immune response. And one of them that we have been doing for a number of years is the sonofoto dynamic therapy. And more recently, the photo dynamic therapy plus, where we're using different wavelengths of light, we're using red light, green light, blue light, and the different benefits of those. Tell us a little bit about your experience with patients with photo dynamic therapy plus Dr. Salimah, any side effects, how they tolerate this therapy. The photo dynamic therapy is very well tolerated. We need to be careful with the IV sensitizers now, with exposure to sunlight. For example, our patients can get a little bit of rash, especially they're incankin and they go to the beach. But it's well tolerated. They may feel a little bit of tingling or a little bit of warmth in the area where the IV is going in. But besides that, they tolerated really good. So sunlight is a photo dynamic therapy too. Yes, it's a lot of plants. And the sonofoto dynamic therapy, we've written about so often and a lot of patient experiences with it. Yes, for sure. And sonofoto dynamic therapy, just to elaborate on what Dr. Salimah was saying, we use something called a photosensitizer, which is also a sonosensitizer. They both get impacted by specific wavelengths of light or sound. And once they get activated, they release what we call reactive oxygen species, which are high energy particles that kill a cancer cell. And since these get absorbed specifically in cancer cells, they leave the healthy cells alone. So it's really a targeted approach to get to those cancer cells. But this particular therapy has got an immune implication that is extremely important. Because the moment these cells die, they send signals to recruit the immune system. So the innate immune system gets activated. The macrophages start gravitating towards the areas of the tumor. And that's when we start having a much larger impact on the cancer than the therapy could have accomplished by itself. You mentioned a key component of the immune system, which are the macrophages. And macrophages are practically in every cell and tissue of the body. They're like sleeping policemen until they're called into action and then they do what they're supposed to do. The Sunni Vera program at Hope for Cancer targets this immune cell called macrophages. Dr. Salinas, you have extensive experience with the Sunni Vera, which is composed of six components. Let's describe the effect of the macrophages. And Shibuta then will go over the components of the Sunni Vera program and bring this together. Well, with the Sunni Vera protocol, we give our patients a molecule that it's an activating factor specifically for macrophages. So basically what we do is we awaken them to start looking for different antigens or foreign bodies in our organism to attack them basically. And being the biggest cell in the immune system and being able to fowl site or eat the cancer cells in these specific subjects, they are very effective in being like the first part of a domino effect of creating an immune reaction. And for that, how important is one of the components of the Sunni Vera program, the vitamin D? Absolutely. The key aspect of Sunni Vera is the use of multiple therapies at the same time in integration with the seven key principles again. So the problem is, for example, comes from B-POL and that is a fantastic product to activate the immune system. Vitamin D is an essential part of this treatment as well. As we all know, pretty much everybody in this world now is as deficient in vitamin D and we all need supplementation on that. But this is particularly more the case for cancer patients as well. In that aspect Shibuta, if I could interrupt for a moment, we need to understand that the considered normal levels of vitamin D by lab are way below what we want our patients to have. So, preferably anywhere between 80 milligrams per deciliter to 100 is ideal of vitamin D levels in blood. If a patient is above 100, all the better. So vitamin D and adequate numbers of vitamin D stores in the body is important. Absolutely. In fact, I was doing an analysis of nutrients through a little program and I was putting in all the food that we eat and some of the vitamin D levels never go anywhere close to our daily requirement. So, we just don't get enough vitamin D from our foods. We're not getting enough vitamin D for some sunlight. Sometimes we get so much sunlight that we get cancer, but we won't get vitamin D. And I would like to mention the orsoda, which is the autologous antigen receptor specific oncogenic tumor acquisition immunotherapy program. And to give this to a patient, we know it's safe because it's from your own body, autologous. We're isolating the antigens or proteins that come from the tumor cells. And we are extracting them from the urine. And then we send this to a specialized lab. When we get the finished product back from the lab, we get bios that are going to be administered intramuscularly. Initially, we start with a lower volume of this immunotherapy program so that we can prep the immune system. And then we increase the concentration on a weekly basis that way, awakening that innate and adaptive immune system so that we could have what we call an antigen antibody response. Simply put. So that the antibodies, surveillance cells can recognize those cancer cells, more readily in mountain immune attack. In addition to the orsoda, we have the helixor therapy. Well, the helixor therapy, something that I liked a lot of it is that we give our patients the dose until we see a specific response, a little bit of fever, meaning that we know that we're giving our patients the right dosage, the dosage that they need. And by seeing that effect, we're demonstrating that we're actually activating the immune system and besides activating the immune system, the concentration of biscuitoxins that it has that are cytotoxic or are specifically to kill cancer cells. So we're getting two birds with one rock there. The key principle of immune modulation brings the seven key principles together because they're all working in synergy with each other. And this was a wonderful discussion how we can regenerate that immune system that God gave us and it knows what to do. But with all the stressors in life, toxins in our environment and antibiotics and aggressive therapies at the Stroy or God Health, we're having a suppress immune system and cancer patients are making it more difficult for themselves to recover and to have that optimal immune system that will give them a more favorable outcome. So thank you, Dr. Salinas and thank you, Dr. Shabito. | ↗ |
| 146 | Thermo Fisher Scientific | How to induce pluripotent stem cells in to definitive endoderm | 491 | 11 | | 50.1 | | 4:03 | In this video you will see how to generate definitive endoderm cells from PSCs using the GIPCO PSC definitive endoderm induction kit. The GIPCO PSC definitive endoderm induction kit is a complete ready to use media system for efficient induction of chloropotent stem cells to definitive endoderm lineage in two days. You can access the product insert and the quick reference protocol online. A supplemental list of reagents used in this protocol can also be referenced here. First, coat the plate with prepared vitro-necked insulation, faw vitro-necked in at room temperature and dilute with PBS. After dilution, add 1 milliliter to each well of a 6-well plate. Incubate at room temperature for 1 hour. Then you'll need to prepare complete essential 8-medium. Find details for this preparation on the web link listed below. Next, prepare a cell recovery solution by adding 250 microliters of Revitis Cell Supplement to 25 milliliters of essential 8-medium. Let media warm to room temperature. When you're ready to seed cells, aspirate the vitro-necked insulation from the coated plate and add 1 milliliter of cell recovery solution to each of the wells. When PSC culture has reached 70% confluence, cells are ready to be seeded for induction to definitive endoderm. Remove, spent essential 8-medium and rinse each well with PBS. 1 milliliter acutease cell dissociation reagent to the well and incubate for 5 minutes, or until the colonies freely come into suspension. Collect cell clumps in a 15-milliliter tube containing 8 milliliters of essential 8-medium. Wash off well with an additional 1 milliliter of essential 8-medium to collect leftover cells. Centrifuge the cells at 200G for 5 minutes. After centrifification, aspirate the supernatant. Flick the tube to dislodge cells and resuspend cells in 10 milliliters of cell recovery solution prepared previously. Seed PSC's clumps at about 1-10 split ratio into vitro-necked encoded plates, so that 15-30% confluence is achieved by day 1. It is suggested that you perform a range-finding study prior to starting definitive endoderm induction to identify optimal seeding density, which will achieve 15-30% confluence by day 1. Faw-diffinative endoderm induction medium A to room temperature. Shake the bottle several times to ensure even distribution of the components in the medium. If the cells are 15-30% confluence, proceed with induction. Completely aspirate spent essential 8-medium from the wells and add pre-warmed definitive endoderm induction medium A. Faw-diffinative endoderm induction medium B to room temperature. Shake the bottle several times to ensure even distribution of the components. Completely aspirate spent medium from the wells and add pre-warmed definitive endoderm induction medium B. After 24 hours, cells are ready to be assayed for definitive endoderm characteristics or further differentiated to downstream lineages. You might observe some floating cells at this stage. These can be easily removed by aspiration without being detrimental to the cells. | ↗ |
| 147 | PromoCell | Mesenchymal stem cells in cell and gene therapy – the immunomodulatory... | 13403 | 157 | 2 | 49.9 | neutral | 2:26 | Since our discovery in 1991, Mizzankomel stem cells, or MSCs, have been used as a promising method to build tissue. However, MSCs can do more for the development of cell and gene therapies. With the latest research, our understanding of the mechanisms induced by MSCs in therapeutic applications has shifted. MSCs also provide therapeutic benefits in the host body by a pair of crune effects and the stimulation of host cells, as they can modulate the innate and adaptive immune responses. Indeed, MSCs not only serve as tissue-progenitor cells, but they also have the ability to alter the tissue environment. How does this work to result in a therapeutic potential? MSCs can mediate immunosuppressive responses thanks to the immunomodulation of monocytes or macrophages, dendritic cells, T cells, B cells, and natural killer cells. As such, MSCs can either directly modify the environment by producing cytokines, chemokines and growth factors, or modify the functions of the microenvironment through the release of extracellular vesicles. These immunomodulatory functions are already helping to develop therapies. Let's take a look at a practical example. Allogeneic MSCs are extracted from donors. These allogeneic MSCs can activate the T cells from the patient and thus be used to develop CAR-T cell therapies. In another example, MSC derived extracellular vesicles are used in clinical trials to treat different diseases, such as severe and critically ill COVID-19 patients. These immunomodulatory functions provide a promising role for the development of more effective cell-engine therapies in treating inflammatory, autoimmune, or cardiovascular diseases, as well as cancer. That's why active research is leading the way to better use for clinical applications of high-quality MSCs in therapies. To learn more about our complete cells and media solutions for MSC culture, visit promosel.com. | ↗ |
| 148 | Harvard Catalyst | Understanding the Spectrum of Translational Research | 27196 | 211 | 1 | 49.8 | negative | 3:21 | Opening a pill bottle and reaching for a medication is easy to take for granite. This simple act is made possible by the work of clinical investigators. But how to treat men such as drugs, devices, and diagnostics develop from an experiment on a lab bench to a product that improves patient health. The process of bringing a discovery from bench to bedside is called clinical and translational research. Clinical and translational research can be divided into four phases or T domains. Each has its respective characteristics, but many researchers believe that their work overlaps into multiple domains. The phases of the T domains are different than the phases of clinical trials, but they follow a similar path. Scientists spend years in laboratories testing a new treatment using animal models. This is sometimes referred to as T0. If the treatment shows promise, researchers will give the drug to humans for the first time. This step is the first phase of clinical and translational research, called T1 research. In this phase, researchers seek to evaluate the safety profile of the drug. To do this, they give the drug to a small group of healthy volunteers to see how the body reacts to it. This research is often conducted through phase one and some phase two clinical trials. To see if the drug is effective, T2 researchers give the new treatment to patients who had a disease researchers are interested in. T2 studies are bigger than T1 with hundreds of people at multiple medical centers receiving the new experimental treatment. These larger studies make up phase two and three clinical trials. The results from these studies help to establish guidelines for how to use the drug in the future. If the new treatment is effective, it receives FDA approval. Doctors can now prescribe the drug in practice and we have moved into the T3 domain. T3 researchers use the guidelines developed in T2 to teach doctors how to administer the drug in hospitals and medical centers. At this point, the new drug is used on thousands of people. Because other drugs may treat the same disease, T3 researchers compare the cost and effectiveness of the new treatment to treatments that already exist in routine practice. Researchers also start phase four clinical trials to continue to watch patients who take the drug to make sure there aren't any negative side effects. The new drug is safe, effective, has been approved, and is being widely prescribed. In the T4 domain, scientists study how the new treatment affects global public health. Researchers continue the phase four clinical trials that they started in T3 and study thousands of people all over the world to see how the drug is working. T4 researchers often observe whole communities to try to figure out what may be causing the disease in the first place. What researchers learn in T4 studies can often even change public policy. The pill has finally made it into mainstream treatment, but the path to get here was not easy. The process of developing a new intervention takes an average of 10 to 15 years and costs at least 1 billion US dollars. It's hard to believe that only a small fraction of interventions make it through all four domains. And most new treatments don't follow the process smoothly in one direction. Often discoveries made in one domain may necessitate that researchers backtrack into earlier phases. Although the road is long, clinical and translational research can have enormous impact on human health. | ↗ |
| 149 | Princeton Spine & Joint Center | Regenerative Medicine- Chronic Low Back Pain #doctor #pain #backpain #... | 4711 | 61 | 4 | 49.8 | neutral | 1:00 | The most exciting advancements for difficult to treat chronic lower back pain is in the bucket of regenerative medicine. Doctors are using approaches like platelet, rich plasma, prolotherapy, mesenchymal stem cells. All of these things can be injected into the back in order to trigger the body, to activate its own innate healing mechanisms. And the results are looking very promising. Now the good thing about regenerative medicine is that all of these approaches are generally safe, and there are lots and lots of anecdotal reports of people who have reported terrific clinical results. The bad things about regenerative medicine are one they tend to be expensive and they're usually not covered by insurance. And furthermore, while we have great anecdotal reports of success, what we don't have are large controlled studies to really know exactly which of these procedures are going to work best for which patients. | ↗ |
| 150 | Harvard Medical School | Reflections on Translational Medicine | 2818 | 29 | | 49.8 | | 3:17 | As you know, there are many challenges facing the production of new therapeutics for our patients. The pharmaceutical industry has been dealing with this issue for many years. I've been thinking about what the major obstacle is. I believe it's not the ability to make molecules to test and to test in patients. But it really is the lack of complete understanding of both what causes diseases, as well as what causes the difference in how diseases manifest themselves. As the problem is very difficult and complex, we need to bring all of our resources to bear on the problem. At Harvard Medical School in the Quadrangle, we have some of the most talented, most brilliant scientists thinking about basic mechanisms of normal biology, as well as disease. But we can't do it alone in the Quadrangle. We need to have partners in the hospitals and associate hospital centers who really understand patients really the best. It's very important that we bring those two major forces together in a collaborative partnership in order to learn about what causes disease and then ultimately make an impact on this important issue. The Harvard Medical School program in Translational Science and Therapeutics focuses on two missions. One is to more effectively or efficiently move ideas to patients. The other part is to focus on a deeper understanding of what causes disease and the heterogeneity in disease. What we imagine are a number of key things we want to do. First, we want to really educate everybody about this process. The second is developing what I call key pillars of science necessary in order for this to happen, which focus on human genetics, on pharmacology, which includes systems pharmacology, chemical biology, the issue of biomarkers and animal models. We want to really understand how we can help the FDA think about regulatory science and also finally, how do we interact fully with industry, with government and non-governmental organizations in order to pull this all together. Ultimately, to take ideas, to help our patients live longer and better lives. | ↗ |
| 151 | STEMCELL Technologies | How to Thaw Human iPSC Lines | 2113 | 29 | 3 | 49.7 | neutral | 5:17 | In this video, we will demonstrate how to thaw the frozen aggregates of a human-induced pluripotent stem cell line. Proper thawing and handling are essential for optimal recovery of your frozen cells, and to ensure your cell cultures are set up successfully. Refer to the product information sheet specific to the cell line you're working with. The latest version of the product information sheet can be found on the product page. For this demonstration, we'll be using the SCTI-003A cell line. For detailed lot-specific information on quality testing results and recommended culture conditions, please refer to the lot-specific certificate of analysis. In a biological safety cabinet, let an aliquot of M-T-ser-plus media and coated culture wear, such as a matrigel-coated plate, warm up at room temperature before thawing the cells. Do not warm M-T-ser-plus in a 37-degree Celsius water bath. Begin by taking the vial from the cold storage unit and place it on dry ice when transporting it to the biological safety cabinet. We recommend thawing one vial of cells at a time. Wipe the outside of the vial with 70% ethanol or isopropanol. Twist the cap a quarter turn to relieve internal pressure, then retighten the cap. The cell thawing process should be performed quickly to ensure optimal cell viability and recovery. For consistent thawing and reduced variability, we recommend using the automated THOST-RCFT2, or you can thaw the cells in a 37-degree Celsius water bath for 2-3 minutes by gently shaking the vial. Do not allow the vial to thaw completely. Instead, remove the vial when a small frozen cell pellet remains. Wipe the outside of the vial again with 70% ethanol or isopropanol. Use a 2-milliliter serological pipette to transfer the contents of the cryo vial to a 15-milliliter conical tube. It's advisable to use a 2-milliliter serological pipette instead of a 1-milliliter pipette to minimize breakage of cell aggregates. Next, add 5-7 milliliters of room temperature M-T-ser-plus. Drop-wise to the 15-milliliter tube, gently mixing the cells as the medium is added. Gently flick the tube to help with mixing the cell's suspension. Centrifuge the cell's suspension at 300G for 5 minutes at room temperature. Remove the tube from the centrifuge, then aspirate the supernatant carefully, leaving some media behind while keeping the cell pellet undisturbed. Add 1 milliliter of M-T-ser-plus to the cell pellet. Then, resuspend the cell pellet by gently flicking the tube, avoid pipetting up and down. Ensure the cells remain as aggregates for optimal attachment and recovery. Next, take the matrijole coated plate and aspirate the matrijole solution from each well. Then add 2 milliliters of M-T-ser-plus to each well of the 6-well plate. Aliquat the cell suspension into the coated 6-well plate containing M-T-ser-plus at 6 different densities as outlined in the cell line-specific product information sheet. Gently flick the tube as many times as needed to ensure a uniform cell suspension prior to seating the cells into the wells. Flick the tube again between seating into each well, as the cell aggregates will sink to the bottom of the cell suspension. The repeated flicking allows for an equal distribution of the cell aggregates between the wells. Place the plates in an incubator at 37 degrees Celsius and 5% CO2. Move the plate in several quick, short, back and forth and side-to-side motions to evenly distribute the cell aggregates within each well. Note that uneven distribution of cell aggregates may result in increased differentiation of human IPSCs, so it's important to move the plates sufficiently in quick motions. Do not disturb the plate for 24 hours. Before performing the first medium change, it's good practice to check the plate using the microscope to confirm the cell aggregates have attached to the matrix. Perform medium changes as needed using M-T-ser-plus? Refer to the M-T-ser-plus technical manual for examples of a flexible feeding schedule. Visually assess your cultures on a regular basis to monitor growth and morphology. This will help determine the optimal day to passage the cultures. For additional information on passaging or managing spontaneous differentiation in your cultures, please refer to the product information sheet relevant to the cell line you are using. And for more information, visit our frequently asked questions page about IPSCs on the Stem Cell Technologies website. | ↗ |
| 152 | NewYorkBloodCenter | NYBCe Dr. Luchsinger induced Pluripotent Stem Cells | 93 | 3 | | 49.7 | | 1:05 | My name is Larry Luxinger and I'm an assistant member here at the Lensley F. Kimball Research institution. I've been with the organization for three years and this is where I started my independent research laboratory to investigate a manoeuvraous stem cell biology. So in addition to that research, I also lead our efforts to create a bank of homozygous HLA and induced pluripotent stem cells or IPSEs that are made from cord blood and units stored here at our National Cord Blood Program. And it is our goal that these IPSE lines are made in a manner that are of a sufficient quality that we would be able to transplant them into patients using cellular therapies derived from IPSEs in the future in the hopes of creating long-term cures for currently incurable diseases. | ↗ |
| 153 | Institute for Neuro-Immune Medicine | The Power of Translational Research | 1327 | 19 | | 49.5 | | 0:46 | One of the things that really was a little bit shocking but impressive to me when I first came to the institute was the concept of translational research. Can you explain kind of for all of our community how that's different than maybe most research facilities? We have a clinic which is really really next door to our research facility. We have a lab. We also have a computational modeling division. So what really happens is that we work in concert. That's critical. It's impressive. It is critical because we want to move the science forward in quick pace. We don't want to wait for years for it to get to a translational space. We have the capability and we are able to do so. This is NSU. Prepare to dominate. | ↗ |
| 154 | In Vivo Podcast | Yamanaka's 4 Proteins: Unlocking Stem Cell Rejuvenation #shorts | 222 | 3 | | 49.5 | | 3:00 | Dr. Yamanaka was the one to show that by introduction of only four proteins, you can revert a skin cell into a stem cell. So how do you see that perhaps playing into these efforts of longevity? I think that's going to turn out to be like very important, huge, you know, reprogramming epigenetic reprogramming. I think it still needs refinement. We've done experiments in my lab, like basically taking progerias, you know, skin cells, bringing them into stem cells. So it works even in progeria. You can sort of, despite the damaged, despite the compromised telomeres, you can still like revert those cells back to the embryonic state. It's interesting. You know, infastinatingly, yeah, this is a good point, like the, so lamin A, the protein that's mutated produces progerin, but interestingly, lamin A and progerin are not expressed in embryonic stem cells. So if you take a skin cell from a progeria patient and reprogram it back to an embryonic form, you're effectively removing the consequence of the mutation, at least temporarily, because the protein is no longer produced in those embryonic cells. So phenotypically, they look normal. You know, they look quite normal at that point. So it gives you an opportunity to go in, you know, perhaps and do gene editing, you know, fix the mutation. And then when you rederive somatic cells from those embryonic cells, they should not undergo early senescence, because you basically fix the mutation at the embryonic. So that's my question for you. When you, when you induce progeria fiber blast back into a stem cell like state, and then don't intervene and then differentiate them again, they then present the same progeria phenotypes before. They do. Yes. Interesting. No, the, yeah, the, you know, because the DNA sequence is still there, and it's going to start making progerian again. Right. And, you know, the cells reacquire the progeria phenotype. And so the gene is silenced when it's in that embryonic state. Exactly. Yeah. Very interesting. Which is kind of like a nice sort of caveat to that reprogramming story, and that it gives you like a temporal window. Because the, you know, to intervene to use CRISPR or something like that, the mutation is not active in that cell type. | ↗ |
| 155 | Abcam | Direct reprogramming of somatic cells into induced neurons | 2787 | 24 | | 49.1 | | 10:30 | Hello, and thank you for joining us for today's webinar, Direct Reprogramming of Somatic Cell into a Doose Neurons. It's the first webinar in the series. It's my pleasure to introduce today's presenter, Dr. Benedict Burninger. Benedict is currently a professor of physiological chemistry at the University Medical Center of the University Minds. Benedict received his doctoral degree in 1996 at the Ludwig Maximilian University Munich for work on activity dependent regulation of neurotrophin gene expression. He then joined the lab of Professor Mumin Poo as a postdoctoral fellow at the University of California San Diego to study fast actions of neurotrophins in synapsis and growth colon. After a brief stay at the Colinska Institute to equate himself with the rapid development of the neural stem cell field, Benedict returned to Munich and eventually obtained a position as a lecturer and senior lecturer at the Ludwig Maximilian University Munich. In 2012, he received a call to the Johannes Gutenberg University of Minds. The work of his laboratory focuses on lineage progression of adult neural stem cells and on direct conversion of brain resident cells into induced neurons. Joining Dr. Burninger today is ours Cracallus, research area marketing coordinator here at App Kim. At this time, I'd like to hand the presentation over to Dr. Burninger. Thank you, Sarah, for this kind introduction. Thanks to App Kim for organizing this webinar and thank you, the audience, for attending this webinar about direct reprogramming of somatic cells into induced neurons. Hopefully, during the talk, it will become clear why I like to start the webinar with a citation from the Earth clinic, a poem by the Chairman, Poit Guter, if you are not willing, I'll use force. It's just what we are telling in a metaphorically to somatic cells when we reprogram them into neurons. This webinar will cover the following topics. First, I will try to explain in a few slides the basic concept on the lying direct lineage reprogramming. That is, the reprogramming of one cell type into another without going through a poor repotent intermediate. Then we will discuss the most common strategy to identify the right reprogramming factors that can trigger lineage reprogramming. This will be followed by an overview over the achievements during the last few years of converting far more blasts into induced neurons, a line of research that has gained considerable momentum. Then I will present you work mostly from my own group, which has focused since quite some time on the possibility of converting cells present in the brain into neurons. First, we will see that astrocytes are an interesting target for lineage reprogramming into neurons. And towards the end of the webinar, we will then look at an example of cells present in the adult human brain that can also be reprogrammed into neurons. And thus demonstrate and further opening potential therapeutic wing those of opportunity. During this talk, whenever I refer to work from colleagues, you will find this citation as indicated here. This figure, for example, is from a review by Sauer Melton. What is lineage reprogramming? Conrad Hall-Woddington coined a classical metaphor for the process of cell differentiation during development. An apigenetic landscape characterized by values of different levels and hills to separate them. A cell is modeled by a marble ball rushing down from the top to the valleys. The pathway takes, decides in which valley it will find a settle, providing a metaphor for the acquisition of a specific cell fate. Since valleys are separated by hills, cells cannot change easily their fate. The green marble represents a pluripotent cell, while the blue marble, let's say a phaboblast. The question now is how to push the cell uphill again. In the case of reprogramming towards a pluripotent state, such as it is achieved by induced pluripotent stem cell technology, you need to push the marble all the way up the way it came. In case of direct lineage reprogramming, often referred to as trans-differentiation, the idea is to directly move from one valley to another. And that's acquiring a new cellular identity. Clearly, this is a very nice image, but how does it really work? Independent of the mechanisms involved both reprogramming strategies promise to revolutionize medicine. Essentially, they represent alternative ways of obtaining desired cell types like hard cells, liver cells, and of course neurons and grier. For the first time it is possible to obtain large quantities of cells of human origin. These in turn can be used for disease modeling and drug discovery, but hopefully one day also for cell-based therapy of the many devastating diseases such as Alzheimer and Parkinson's disease. Now back to the mechanism. Simply far we can look at it this way. Each cell fate is characterized by a regulatory network of factors, typically transcription factors that maintain a specific state through reciprocal feedback interactions. This can be called a program, let's say green. Now to change to a program red, we must activate new nodes in the network that were inactive when the cell was enacting the program green. This may be done by overexpressing transcription factors or microRNAs. During successful reprogramming this will now lead to the progressive stabilization of a new network of interacting factors. Depicked in red and a deep stabilization of interactions that characterized the state green. Now what is the basis for selecting the right factors? As I'm also a lot from Harvard University discuss in the recent science review, a good choice for the right reprogramming factors is inspired by development. Factors that drive neuronal specification in the developing CNS are good candidates for reprogramming other somatic cells into neurons in vitro and perhaps also in vivo. The other big question concerns the cellular target or which cell type you want to reprogram. This can include cells outside the CNS such as skin phyroblasts. But if we want to move reprogramming into the vivo setting, we must select cells that reside in the brain such as clear or as you will also see non-neural cells such as perisides. Back to the factors. One way is to identify transcription factors and one way to identify transcription factors and microarrays that can be used for reprogramming is to screen for them through microarrays or RNA sequencing within the embryonic brain tissue. From these you can now obtain an arsenal of viral vectors, lentiviruses or retroviruses and in fact you're starting cell population of choice. So sometime during which reprogramming should take place, you start to evaluate the outcome and conduct functional assays such as patch clamp recordings in case you try to obtain neurons to prove that cells really change the identity. What are the criteria for a cell to fulfill to be called a neuron after reprogramming? First, the phenotype should be stable even once the reprogramming factors are switched off. Of course at the same time the properties of the cell of origin should have been lost by the cell. Otherwise this would indicate incomplete reprogramming. In case of neurons it is very important also to derive cells of a specific subtype. For instance if you want to model Parkinson's disease you may want to specifically generate midbrain dopaminergic neurons such as occur in the substantiomagra. Finally, these cells must exhibit the electrophysiological characteristics of you decide top of neuron. | ↗ |
| 156 | TEDx Talks | Disease avatars : Chasing precision medicine through cell reprogrammin... | 1615 | 19 | | 49.0 | | 14:15 | What I would like to do today with you is to walk with you through a frontier in medicine and to share with you the excitement for how this frontier is enabling us to ask new questions about health and disease to interrogate in new ways our bodies in space and time. It is a frontier that is enabled by a transforming technology, a real radical breakthrough called cell reprogramming, but it's about so much more than just technology because it's about changing our gaze, the way we look at patients, the way we look at ourselves, and it's something that is going to affect our lives in our lifetime. So changing about gaze, it's basically about going from living things out, from excluding things that are put in them in brackets to include things, to bring them back in and in fact to the fore in the petri dish of a lab with very important clinical implications. What do I mean by that? Well, let's go to Meshephokol who is an archaeologist of knowledge, that's how he defined himself, and who was looking at how medical doctors looked at disease and patients in the 19th century. But that gaze is still very much with us, except that it's a legacy under strain. So in his words, to the pure and nozzological essence, so to the essence of disease, the patient adds his predispositions, his age, his way of life, and the whole series of events that appear as accidents. He who describes a disease, so the medical doctor, the physician, must take care to distinguish the symptoms that necessarily accompany it and which are proper to it, from those that are only accidental, such as those that depend on the temperament and the age of the patient. It's of course the language of their time, but the punchline comes here. Paradoxically, in relation to what he's suffering from, so the disease, the patient is only an external fact. The medical reading must take him into account only to place him in parenthesis, right? So we are looking at patients, but since we are thinking about diseases, the patient in its individual configuration must be bracketed out. Right contrast with the view of precision medicine. This is a website from the initiative that Obama launched last year. Several similar initiatives have, I mean, well, flourished around the world. And the idea here is that the things that we had to brag it out are actually the very things that we want to focus on. And this is becoming possible to envision through the conflation of a number of technologies. First of all, on the one hand, the possibility to sequence very fast at an affordable price our genomes, so to actually read our DNA. On the other hand, the amazing capacity to compute large amounts of data is the so-called big data deluge that I'm sure you will have already heard of. But today I'm going to focus about what is here in the middle. One of the enabling technologies that allows us to bridge the gap between genes and the environment, genes and clinical data. And that is every programming. And so I would like, first of all, to thank my team members because it's important to realize that in science, when we change the game, we change the game in a team. And to paraphrase new term, we actually change the game only on the shoulders of giants who have changed the game before us and in fact, who set for us the table on which we can start playing the game to start with. So this is my team in Milan. And giants of game changing, like Corridd Woddington, in the 50's gave us tools for thinking about development by making an analogy of the very first cells in the early embryo to a marble that is sitting at the hill. And it has various options in going downhill. And these options are the various fades that can happen to that cell. It could become a neuron, it could become a skin cell, it could become muscle. And of course, you see that it's downhill. So the analogy here is between a development and gravity, a process that once it unfolds, it is irreversible, it can only go downhill. To the extent that another giant of game changing, Spayman, reminds us that we are standing and walking, like me now, with parts of our body which could have been used for thinking, had they developed in another part of the embryo. So crucial moments at the top of the hill, very early on, cells are still very plastic, but those decisions will unfold all the way through. Now the game has radically changed. It has radically changed thanks to decades of research which culminated in the towering achievement of Nobel Prize Shinya Yamannaka 10 years ago, who showed us that by tinkering with just very few genes, four genes out of the 25,000 that we have, it was possible to reprogram a fully specialized cell, like my skin cell, that only knows how to behave as a skin cell all the way back to the top of the hill, to bring it to that stage so that now, in vitro, in that pit redish I was telling you about, it can actually be moved forward again. So we go uphill and then we can go downhill again, but we can do it in vitro. What are the implications? Well, the reason why this is changing medicine is because this is actually enabling to make the body outside of the body. What has been the problem so far, the key rate limiting step in medicine, not having access to the cells that we most wanted to have access to, the disease cells of a patient? Well, because quite obviously these cells are inside people's bodies. Think about brain, but in fact, for most of the diseases, these walls and remains a fundamental problem. Now however, you can actually externalize tissues and cells of the patient. Because what you do is you reprogram skin cells, you have these induced pluripotent stem cells, they are induced because we induce them to do this transition, they are pluripotent because they are at the top of the hill, so they can do all the tissues of our bodies, but in vitro, and they are stem cell because they can keep doing it basically forever. Once we externalize, once we bring them outside, they are immortal. And so in the dish, we can build avatars of our tissues, representations of our tissues in both health and disease that we can mine and probe for a number of medical questions. And of course, it could even be possible that some of these cells then can go back into the patient to regenerate parts of its alien bodies, but today we are focusing on what we can learn outside of the body. So what does the eye in IPS really stand for? Of course, the original meaning is induced because we were downhill and we induced them to go back up. But of course, you can't help notice how that eye resonates with so many small eyes that label the devices that populate our digital social life. Starting, of course, with the internet, one of the words that Steve Jobs mentioned in his speech in which all of these small eyes were actually connected to the launch of the eye-mac, and the internet with the idea of the constant connectivity. And if you think about it, these avatars are actually all the time potentially connected to us because once you reprogram from your skin these pluripotent stem cells, they are there. They can be banked, they can be stored in lab, and you can go back to them to ask medical questions because these cells have your genome, and these are the cell types that you want. And of course, information, because it is true that in a couple of days we could sequence the genome of all of us here today, but the truth is that we still understand very little of that information. And the only way we go about closing that gap of knowledge is actually having a system in which we can experiment on that level of information. And now we have the way to do it because it is outside of the body. I don't think I need to tell you why it is inspirational. You just need to look at me and to how I'm excited about these developments in my and several other labs. And of course, the individual, because this is the thrust of this frontier. Thinking about that patient going from being within a bracket and being left out to actually coming to the fore in a petri dish in a way that samples the specific configuration of each one of us for a range of medical questions throughout our lifetime. So the challenge, of course, is monumental because we have clinical data, we have genetic data, and we need to bridge them in vitro through a number of molecular features that we have to see and discover in these avatars of ourselves. And so I'm just telling you very briefly towards the end, what we are doing in the lab in which we study cancer and neurodevelopmental disorders or intellectual disability and autism. And they're going to tell you just about a pair of diseases and just to make sure that we are on the same page. Because all of ourselves have 46 chromosomes, these contain about 25,000 genes, the two diseases I'm briefly telling you about are due to the fact that very few genes, about 26 from chromosome 7, are actually present either with one copiless or one copi moor. So most of us have two copies of each gene, including these famous 26 genes. But children with Williams syndrome have one copiless. And children who have one copi moor, so who have three copies, end up having autism or attenurate a severe speech impairment. So these are two conditions that give us also an incredible glimpse into foundational traits of the human condition, like the acquisition and use of language and the acquisition of social interactions. Williams children are gregarious, hyper sociable, the clinicians used to refill them as having a coptile party personality. If you have one copi moor of the same genes, so a very subtle change, you end up with autism. So this is just a more detailed view because it's not only about cognition, but it's also at the level of the facial features that changing the dosage, the quantity, the amount of genes, or very few genes, ends up in having these symmetrically opposite phenotypes. So what we did was to actually reprogram skin cells from these patients and their families and build these avatars. And then ask the questions. Once we have brought these cells back to the top of the hill, like the marble I showed you, what can we learn? What is the impact of having one copiless or one copi moor of these apparently fundamental genes? Well, we discovered surprisingly that already very early on, already once we added the top of the hill, we find major alterations caused by these imbalance in dosage. And the desalteration then is amplified as you go down the hill. So the problem is seeded very, very early on when you are at the top of the hill. So this is then a summary of our project and these kind of projects which can really be applied to any kind of disease that has a genetic component. Here you have a disease that has a combination of features. You can now resolve them. You can destructural them in vitro by building from that patient with that genome, with that disease, the tissue types that together then you can reassemble to start the both these disease is really about. And in fact, I refer to this as the factory of avatars because this is for example an induced purportant stem cells that we reprogram from one of these patients in the lab and we are able to push it in vitro towards the progenitors of the face, right here or towards the neurons of the cove text. To the extent that now this is very recent data from a lab, we and others are actually pushing a new frontier which is making from these cells not just neurons but three dimensional aggregates that mimic the development of the brain cove text in vivo. But it's happening in vitro. So we have models avatars which recapitulates the step in which we form a brain but again outside of the body. And so I would like to finish with Archimbaldo, a real game changer in art where this amazing skill of capturing humanists, features of the human condition, not only of human anatomy, by assembling other aspects of life and sometimes even all life in a way that at the end you actually reconstructed this model of humanists. And the technology I told you about today which is really a foundational tool for precision medicine is about capturing the humanists, the humanists of a specific patient in a dish by resolving and deconstructing the disease and then bringing it once back on into a coherent hole. A very exciting time which again will hopefully affect all of us because it will give us new tools to push ahead this frontier. Thank you very much. | ↗ |
| 157 | NCCIH | Research on the Potential Immunomodulatory Properties of Probiotics | 5957 | 19 | | 48.9 | | 11:21 | And as Dr. Killin mentioned, our research is also highly related to the FDA. Our research is under investigator initiated IND because clearly the goal of our research is to prevent treat mitigate or cure relating to the prevention and treatment of infectious diseases at the extremes of age or in immune compromise. So we are very much under regulation from the FDA, which has changed dramatically the way we move forward. So in 2006 it was also simple. I was very, very fortunate to get this NIH grant funded and the concept here was simple. Elderly people do not respond well to the flu vaccine. They need some help. Probiotics may have some immunomodulatory properties, but the idea that probiotics would actually benefit a flu shot was a little far fetched. However, what about that mucosally administered flu vaccine that clearly has a site of action in the mucosa where the probiotics have a site of action? Is it possible we could boost the immune response of the flu vaccine for elderly subjects? So we were very, very excited to talk to the FDA and they said, no. Recently so, their argument was, you've got to show that this product is safe and also how the heck do you know it's self in the elderly? Have you really thought about that? And the answer was probably not as much as we should. So what the FDA asked us to do and I'm going to report a little bit of data on today is first do something just very, very simple. Can elderly people safely tolerate a probiotic over a short period of time? And if they can, then what I'm going to do is move ahead to see whether or not administering the probiotic with the flu shot helps. Honestly, didn't really expect it would. But then and unfortunately at the end of the flu season because the flu mist is not approved for people over the ripe old age of 49, out. The bottom line is we then wanted to move ahead with this to evaluate safety and preliminary immunogenicity and to potentially study the mechanism of action of the probiotics in this particular circumstance. Then, and this is where we are right now, we can go back and talk to the FDA and see what they think about proceeding with the original study. So that open label study in elderly people, we found 15 of them aged 65 to 80. It really is amazing how many people truly think they're healthy yet have a large number of conditions. We have people who came in, we asked if they had diabetes. No. What meds are you taking? Insulin. Well, don't you have diabetes? No, the insulin cures the diabetes. I don't have diabetes anymore. So you've clearly got to really do these studies properly in order to make sure you have healthy people. But I was also amazed to find individuals 80 years old who aren't on a single medication. It happens. We had these subjects consume lactobacillus GG, a fairly high dose for 28 days and then we followed them for another 28 days. We followed their safety on a daily basis, prompting them if they had abdominal complaints or any other issues. We then called them up, we had study visits and in this circumstance along with Dr. Fraser, we were able to do some of the microbiome and omics studies and with Dr. Gloria, we were able to do a whole blood cell transcriptome studies. Our safety data are honestly, moderately boring, but that's good. I will tell you one of the things we are very good at is we really like to follow up these subjects and we actually have great track records. The type of subjects who participate in these studies often love these studies. They love filling out their daily diaries. Oh my goodness, when we stopped asking them for the daily diaries, many of them were crushed. What were they going to do? But clearly, when we're asking people all the time, if they have any side effects, we are going to get them and yes, in 15 people, 47 side effects sounds like a lot, but they were all mild meaning they did nothing. They didn't take meds, they didn't go to the dock, nothing else was going on and we did have just one severe unrelated adverse event in somebody who passed a kidney stone, but other than that, totally trivial side effects. What this slide shows in collaboration with Dr. Gloria is that if we actually look at the LGG in the stool that we get from these subjects and this was at day 28 and they were moderately compliant, there was only one subject who was not compliant at all, there's a lot of variability in the number of counts of LGG using PCR, which does pick up dead and alive organisms, but also if you do routine culture, you'll also see there's a lot of variability. Does this matter? I don't know, but this is one of the things that we are delving into right now and has not been well addressed in the literature. So the recovery of LGG is variable by subject and it also is not the same by method because the methods are doing different things. This work done with Dr. Fraser at Maryland basically is the 16S ribosomal RNA information. So it's not that whole set of gene information, it's a more limited set. And what this shows is these are the three days, baseline day 28 and day 56 and that's repeated for each of the subjects. And I think you can see overall this looks incredibly boring, like there's not much going on at all. And if you focus on the phylogenetic diversity over here, which is ranging from 20 to 40%, you'll see it mostly bounces around and stays flat. So at the 16S level, give people LGG for 28 days, not much happens. This guy is mildly interesting, he was prescribed CIPRO and his diversity dropped dramatically about six weeks into therapy. So that was the most exciting thing that we found as far as that was concerned. This again is a representation of that 16S data. But then what Dr. Fraser did was the whole gene data. And can you see the patterns in general are similar, but the data are different. Again telling us we've got to be awfully careful what we're looking at. And we really need to understand the questions that we are asking. The thing that was very interesting here is we're picking up all this yellow stuff. This yellow stuff are the archaea, not in everybody in seven of the individuals, but it doesn't look like it's changing in any particular way. What are these archaea doing? Again something pretty interesting. And then this is really cool. What Dr. Fraser did was look at the LGG itself. Is there anything going on with LGG baseline? No. On day 28 all these yellow indicate that the probiotic is actually making copies or there's in vitro expression of the genes involved in LGG. The only person that we didn't find any expression in was somebody who wasn't taking it. That's a relief. And on day 56 gone. So three different ways of looking at the data telling us different things. But what this probably tells us, the idea of lobbing in LGG, changing what's going on in the gut in terms of the bugs that are there, probably not going to happen. But it doesn't mean that there aren't subtle effects. And these data from Dr. Gloria's lab are also very interesting. These are Paxstein RNA from the host. So we're now looking at the host immune response. Remember these were healthy elderly people who just took LGG. There was nothing going on. We weren't treating anything at all. But there was differential expression at day 28 versus day 0. And the gene that struck out the most in this circumstance happened to be a gene that was downregulated related to the regulation of IGE. The consequences of this again were investigating further. | ↗ |
| 158 | Pharma Research Simplified | Immunomodulation | 1977 | 20 | | 48.8 | | 13:09 | Hi, today we will see about immunomodulation. So immunomodulation means modulation of the immune system, modulation particularly means regulatory adjustment. So as a part of immunotherapy and according to therapeutic goals, immune responses are either induced, amplified, attenuated or prevented. So this immunomodulation therapy involves therapeutics which are called as immunomodulators that are substances that help to regulate the immune system. Concept of immunomodulation. It involves non-specific activation of function and efficiency of macrophages, granulose diet, complement, natural killer cells, lymphocytes or production of various effector molecules which gives protection against bacteria, viruses or fungile. So that is alternative to conventional chemotherapy. Diseases related to immune system dysfunction involves inflammatory diseases, autoimmune diseases, infectious diseases, orthodox clearosis, hypersensitivity and cancer. Autoimmunity means inappropriate reaction to self-entigen. So examples of autoimmune disorders includes mayas, thinnium, gravies, typhoon, diabetes malitis, systemic leopards, arrhythmic metasus, grieves disease, celiac disease, pernicious andemia, dimadied arthritis, multiple sclerosis, hypersensitivity means hyperactive immune response. The treatment of inflammatory and immune related diseases due to defects or disorders of the immune system necessitates the modulation of the immune response. So immune system involves two components that is in it in immunity as well as adaptive immunity. So in it immunity protects against pathogen, then it will stimulate adaptive immunity. Also in in it immunity protects pathogen which is most rapidly acting depends on neutrophils, spectrophages, dendritic cells and monocytes. Among these all leukocytes, these are all leukocytes which perform phagocytic activities. By chemo-taxis leukocyte predation and pathogen engulfment which leads to intracellular killing and ultimately results is elimination of pathogen. Also from that macrophages are involved in the release of nitric oxide by inducible nitric oxide synthase. Also macrophages modulate adaptive immunity by presenting antigen to CD4T cells through major histocompatibility complex to antigen. Also CD4T cells perform their functions by TH1, TH2, TH17 and TH3D4T reglit results. Also they help B cells develop into plasma cells and activate T cells to become activated cytotoxic T cells. Adaptive immunity which is responsible for enhancing the protection which involves mainly two cells that is T cells as well as B cells. Leucocytes perform phagocytic activities as I told you that is chemo-taxis leukocyte adhesion and pathogen engulfment. First one is chemo-taxis performed by leukocytes. So phagocytes migrate towards chemo-adractant such as complement C3A and complement C3B and formal metheonyl-luosyl vinyl alanine which is a bacterial product. So chemo-adractants utilize a similar signal transduction system that is G-froutine coupled receptor involving platelet activating factor receptor, formal metheonyl-luosyl phenyl-aneline receptor and complement C5A receptor. So interaction of chemo-atrector and its receptor stimulates cytoskeletal reorganization, calcium mobilization, de-cranulation in heterologous cells types. Next function performed by leukocytes is leukocyte adhesion which is initiated by selection interaction followed by the interaction of leukocyte integrain of the CD18 complex on the surface of phagocytes. So phagocytes is of microorganism, triggers super-acid radical generation which releases reactive oxidants which is such as hydroxyl radical, hypoclores acid, chloramides, through the activity of myeloperoxidies. So the basic mechanism by which the house defend the body against infection involves destroying the pathogen or either by enhancing the body's immunity. Plants are the integral and essential part in complementary and alternative medicine due to their ability to develop formation of second remittable, like proteins, flavonoids, alkaloids, steroids and phenolic substances, forms of immunomodulation. So immunomodulation involves both natural as well as human induced modulation and thus the word can refer to homeostasis and immunomodulation. Animal models use to study immunomodulatory activity. This one is cyclophosphoid induced immunosuppression model. It can be performed in Swiss albino mice or in rats. In Swiss albino mice cyclophosphamide is given at the dose of 30 milliampere per body weight through IP route. So dose may vary depending on duration. Cyclophosphamide is alkylating agent used in antinoblastic therapy such as lymphoma, myeloma and chronic lymphocytic leukemia. It acts as on both cyclic and intermitotic cells and results in dupletion of immunocompetent cells. Immune parameters or ICs. So evaluation of immunomodulation involves either hematological parameter assessment, lymphrofil adhesion test, complement C3, IgM level, favoritivity activity, SOD level or lassozyme activity. In vivo-Ssays involved, estimation of specific antibody profile and title to specific response, delayed type hypersensitivity response. Splin-focci which is also called as colon deformation has saved for immunostimulant activity. Immune or progression of auto-human disease in experimental animal models for immunosuppressant activity. Prevention of allographed or gene-ographic rejection. Evolution in drug-ent malaria and Japanese encyclitis virus models for immunostimulant activity. Immune or modulatory activity in functional assays involving X vivo or in vivo experiments involves stimulation of peripheral blood mononuclear cells, cytokine release in mononuclear post-inluptocytes, T cell stimulation, activity of monocytes, natural killer cell activity, tissue culture virus challenge, antitumoral activity of stimulated Cera and granulocyte activities. So what are cytokines? These are no molecular weight proteins which includes interleukines, interferons, chemokines, monokines and certain growth factors. They play a significant role in co-ordinating early responses of monocyte microfages, beneratic cells and lymphocytes. Also stimulating facoside migration, initiation, recognition, regulation of the inflammatory cell process and they also serve as an important component of innate immunity. So there are two types of cytokines that is two inflammatory as well as anti-inflammatory. Pro-inflammatory cytokines involves two more neck crosses factor alpha, interleukin 1, interleukin 6, interleukin 18, interleukin 8 and anti-inflammatory cytokines are IL-4, IL-10 and IL-13. Two inflammatory cytokines released is regulated by NF-CAPAB that is nuclear factor KAPAB and mytojan activated protein kinase pathway. So immunomodulation involves increasing WBCRPC percentage hemoglobin and percentage neutral field addition in case of hematologic parameters. Imminomodulate reactivity through the regulation of cellular process involved in inflammation involves NF-CAPAB signaling in plamozum activation and autofagy flux. Imminopathology of coronavirus disease 2009. That is weak innate antiviral responses as a result of inadequate production of the antiviral cytokines that is type 1 and type 3 interferons. Imminoblast flow inflammatory responses with high levels of chemokine, unsyptokine expression. Immune related signaling pathways and genes. So there are three main pathways involved regarding immune regulation involving nuclear factor KAPAB, activator of transcription and signal transducers. Another of transcription involves stat pathway, PPAR1, pathway, mechanistic target of repamacing, extracellular signal regulated kinase, AMP activated protein kinase, immune related genes, IL-1 beta, TNAB, FAM, MYD88, MX1. These are the genes involved in immune regulation. And that, mixed virus resistant 1 protein facilitates defense against a diverse range of viruses. Whereas, myelod differentiation factor 88 plays important role in host defense against bacterial infections, which is important adaptor molecule in the toll-like receptor signaling pathway. Approved drug with the immunomodulatory effects. So there are two classes of drugs approved for the immunomodulatory activity. That is treatment of common diseases involving drugs like statins, metformin and juteinsin receptor blocker and anticancer drugs like thelidomide and throcycline, demethylating agents. Imminobodulatory effects of drugs for effective cancer chemotherapy. Immunovotorosis in cancer immunotherapy includes immune checkpoint inhibitors and adaptivity cell therapies. Immunovotorosis in inhibitors consists of monoclonal antibodies, which make them highly expensive. So improved cancer outcome can be given by altering patient's immune-sufferative status or by enhancing anti-tumor activity. Still, many cancers with no cure. So enhancing anti-cancer immune immunity will play an important role in cancer treatment. Thank you. | ↗ |
| 159 | Thermo Fisher Scientific | Advances in Stem Cell Research: Cell Reprogramming with Episomal iPSC ... | 4214 | 20 | | 48.6 | | 2:39 | [Music] reprogramming you know we're talking a science here that's only a few years old but the truth is that reprogramming in itself isn't that difficult if you willing to put the effort in just to develop your method we're pretty good at it now and it's a really reproducible method there's really almost no reason to be doing it in it the system that leaves insertional mutagenesis as part of the backround we can't build a standard method if your goal is to make ad do anergic neuron from 10 different individuals if every clone you make has a variable number of the reprogramming factors inserted in variable location with variable silencing um and then you add on top of that all the other variables in this science and you you can't make a reproducible population of dop energic neurons [Music] there's several different ways you can do this footprint free episomal we think works really well um we get footprint free colonies we get the numbers you'd want and they're fully plur potent and when you use episomal reprogramming in combination with a defined feeder-free system like the vittin and like essential 8 you end up with a more stable platform the colonies tend to be the same every time they tend to behave the same CDI prefers the episomal vectors because it's a very straightforward technique it's a single transection it's a nontoxic reagent it's just DNA you don't have to handle viruses that are potentially pathogenic you don't have a workflow that requires you to transfect the cell nine times in a row on nine different days you've got a somatic cell you transfect it you wait 16 to 20 days you pick colonies and it doesn't leave a residue it's pretty well documented at this point that there's examples now of fully sequenced genomes where it does not get integrated and doesn't leave a residue we can measure for its loss over time so it's a beautiful reagent you use it it does its job it goes away after the transection we have pretty good data now showing that you can go directly into vitr and you can go directly into E8 we've done E8 lots of times cells grow they behave can reprogram directly into that defined media [Music] | ↗ |
| 160 | University of California Television (UCTV) | Stem Cells and Next Generation Regenerative Medicine Therapies | 39783 | 963 | 41 | 48.5 | positive | 59:32 | No transcript | ↗ |
| 161 | Integrated Orthopedics Brian Gruber, MD | Regenerative Medicine in Orthopedics & Sports Medicine | 3909 | 18 | | 48.4 | | 3:14 | Everything in orthopedic surely is about getting things to heal. Under genitive medicine you're using your body's ability to heal itself. We do PRP as well as stem cells. This can be to say avoid surgery or in the surgical setting you can actually augment or improve the heal rate of many of the operations that we're doing. Over the years my knees have been aching but there's a fine line between pain and aches and getting through your usual triathlon blues. I did a triathlon in which I had a lot of pain both during the swim and particularly the bike ride and the run and I went to see Dr. Gruber. We looked at the knees and we found if I had a lot of issue with the cartilage that was left in both knees and it looked like I had some arthritis going on. They're unbeknownst to me. Some of the common things that we're dealing with is arthritis. We're doing PRP and stem cells for knee arthritis, hip arthritis and shoulder arthritis. We're also treating a lot of situations concernedively. If somebody has a partial tear of maybe a rotator cuff tendon or a biceps tendon there are certain strategies and certain techniques with biologic medicine that we're doing to try to keep patients out of surgery. So we're excited about that. As we were learning what was progressing with my knee I was given an option to do PRP and H.A. When I got the injections I felt some relief in the first two weeks just a little bit. I don't know if that was a result of the PT and maybe some healing of the knee but in the next coming months I had a lot less stress on the knee, a lot less aches. It does give relief and I know we'll help with the arthritis in both of the knees. The procedure itself is done in the office. Patients will come in after we've determined their appropriate candidates. With you a blood draw we take about 15 CCs and we spend down the patient's blood. So what you're left with PRP which is platelet rich plasma. You have a whole host of things most importantly the platelets which house growth factors and really everything that we think is important and crucial in allowing tissues to heal. The patient will be in the procedure room and then we'll inject under ultrasound the involved joint rotator cuff or whatever it is that we may be treating. If we end up going to the operating room for example the rotator cuff there's improved outcomes with augmentation of rotator cuff repair surgery with stem cells. I initially began in the OR however we have moved this over to the clinic setting as well. Majority of the stem cells that I'm doing currently are bone marrow harvests. We're able to do this very comfortably you know in the clinic setting in our procedure room. In fact I'm surprised myself that patients were able to tolerate it so well but they are. The most rewarding thing really is getting patients back to doing what they want to do and that's pretty plain and simple because that's why they're here. You know they can't play a sport and they can't play pickleball they want to play pickleball they can't hike and now they can hike. So I mean that's pretty basic but pretty you'll fund a mental and orthopedics and orthopedics is a specialty it's really what it's all about it's about function and quality of life and if you're able to deliver that at a very high level then your patients are typically very happy. | ↗ |
| 162 | Boston Children's Hospital | induced pluripotent stem (iPS) cells: Part 1 | 7274 | | | 48.2 | | 2:50 | We have two different types of stem cells, the traditional embryonic stem cell, which comes from early human embryos, and this new form called the induced pluripotent stem cell. By calling it pluripotent, we recognize that it has the ability to make any tissue in the body. A property that previously we thought only embryonic stem cells had. Now importantly, they're not identical, and we're still learning whether or not the induced pluripotent cells can be a full replacement for embryonic stem cells. They may one day, but certainly for the foreseeable future, we're going to move forward studying both types of stem cells. A little over two years ago, a Japanese scientist named Shinny Amanaka discovered that if you took a small set of genes, which are normally expressed in embryonic stem cells, and you made them expressed in skin cells, it would turn the skin cells into embryonic stem cells. These are the so-called IPS cells, the induced pluripotent stem cells. There's been a natural evolution in the technique itself. The practice that Shinny Amanaka introduced two and a half years ago was to carry these reprogramming genes in via viruses. The problem is that viruses insert themselves into the cells DNA and can act as mutagens, it can actually induce the cells to become cancerous. So over the last couple of years, we and others have been working on ways of eliminating the viruses from the system. And now we have a new improved approach where we can say use a virus to carry these reprogramming genes into the cell, affect the reprogramming, the reversion to the embryonic state, but then we can remove the viruses. And that's one technique that we practice that leaves us with a viral-free cell, which is a pristine cell that we can now study, and it would be a cell that would be safe to put back into a patient. The real long-term hope, though, is that we don't have to use viruses at all, that we could identify drugs which act on the same pathways as the viruses to reactivate this embryonic or pluripotent potential in every cell. Initially, we expect we'd do it in a petri dish, but maybe in the long run, we'd even be able to learn how to affect these changes or transitions and cell fate in the actual identity of a cell from one type into another in your own body. That would be cell therapy, that would be the realization of one of the great ambitions of regenerative medicine. | ↗ |
| 163 | Michigan Center For Regenerative Medicine | Highly Effective Arthritis Treatment with Regenerative Medicine | 107 | 2 | | 48.1 | | 0:54 | That's profound because I think a lot of people, there's a lot of people out there that are looking for options in the medical world that do not involve the letter S like surgery, right? They're looking for not just another drug to put in their body too, but something that actually addresses the root cause, the problem. I know that's certainly what we try to do on the movement side of things, but it's an interesting example to use that. Are you saying that regenerative properties that you inject help to use the word tighten, I think is what you said, right? They actually help to change ligament through stimulating collagen formation. So it activates fibroblasts which are cells that make collagen. Collagen is a protein that gives structural integrity to over connective tissues, so things like ligaments, tendons, cartilage, and it stimulates that collagen formation, which essentially tightens the rubber band. Yeah. | ↗ |
| 164 | University of California Television (UCTV) | iPSC derived Cardiomyocytes for Predicting and Removing Drug Cardiotox... | 1286 | 14 | | 48.0 | | 14:16 | Hello, my name is Mark Marcolla. I'm a professor of cardiovascular medicine at Stanford University. It's a pleasure to talk to you about using induced pluripotent stem cells or IPSCs for predicting and removing drug cardio-toxicity. This work has been supported for many years by Syrim. We're very grateful for that work in establishing this platform in my laboratory. So what is drug-induced cardio-toxicity? This is the unintended adverse effect of medicines on the electrical and or the mechanical function of the heart. This can be a very major problem for certain areas of medicine such as oncology, where as many as a third of the patients who have been treated with oncology drugs will develop some form of heart disease as a consequence of their treatment. It's also a major problem for pharmaceutical companies. It's the major reason for drug attrition, the drug failure during the development, and in some cases even after market launch. So we are using IPS cells to try to address this problem. So what IPS cells are cells that we can derive from your skin or your blood, any other cell type in your body basically, by reprogramming them back to an embryological state. This was first done by Shinya Yamanaka, based on work done by John Gurdon years before. And the technology for this won them the Nobel Prize for Medicine in 2012. So once we have IPS cells which resemble cells of the early embryo, we can direct their differentiation to different cell types in the body such as heart muscle cells, brain cells, kidney cells, intestinal cells, and so on. And so you were able to study disease because of course these cells retain the genetics of the original persons of the person as a genetic disease. You hope that some manifestation of that disease will be reproduced in the laboratory. And we can also study the effect of drugs on those cells. So using this platform then, the work that I'm going to tell you about creates muscle cells, heart muscle cells, and you can see that in the video on the slide. We treat those heart muscle cells with drugs or drug candidates. And in order to predict the adverse effects that those molecules will have on the heart, as well as to understand the influence of patient genetics, some people are much more susceptible than others to the adverse effect of drugs. And we also would like to use this platform to engineer safer drugs. So my talk today will be divided into three parts. I'll first talk about our recent work to develop efficient means of producing and increasing the fidelity of disease modeling and IPS cells. Secondly, I'll talk about using this platform to optimize an existing drug for a cardiac electrophysiologic disorder. And thirdly, I'll talk about our work to reengineer an oncology drug to diminish its adverse effects. I'll start with the first part, producing cardiomyocytes efficiently and making better disease models. So when we began this work with serum funding back in 2008, it was only possible to make small numbers of cardiomyocytes, certainly nothing that could be used in high throughput drug screens. So with grants from the serum to John Cashman, a bit of medicinal chemist at the Human Biomelecular Institute. And to me, and I was in those days at the Sanford Burnham Prebis Institute and at UCSD in San Diego, we developed a screening platform where we could look for compounds that would drive stem cells in those days embryonic stem cells to form cardiac muscle cells. And we hit upon a number of compounds that would do this, one of them is shown here. And these molecules are now the basis of nearly all efficient protocols to produce cardiomyocytes. More recently, we've been using this platform to advance the maturity of cardiomyocytes, IPS cardiomyocytes. These cells, if we form them by conventional means, are similar to cells of a very, very early embryo for a few weeks a month or so into gestation. And that hamper's disease modeling, which of course were interested in the adult. So we learned that if we switch the energy substrates that the cells burn, so rather than burning sugar, we switch them to fat and other substrates. Now we can drive the metabolic, the structural and the electrophysiological aspects of their maturation. And that improves their ability to model diseases as exemplified by dilated cardiomyopathy or an electrophysiological disorder long QT syndrome type III. So now, in the rest of the talk, I'm going to talk about our efforts to use this platform for drug reengineering. And the idea here is to make a better version of a drug that has some adverse effect on the heart of a patient that limits the, either the dosing or compromises the patient's health. And so the idea is that we would create heart cells from these people who have problems with some drug. We would then, in the dish, visualize the effect of that drug on the heart cells. And then we would, using high throughput screens, using robotic platforms such as what you're seeing in the video, we would then develop better versions of those drugs, understand what to tweak in the drug to make it safer and yet retain its activity. And that would then return that, the idea would be to return that drug through a pharmaceutical development pipeline back to the patient. But the problem when we started this, it was a rather audacious goal. Because IPS cardiomyocytes had never been used to drive a drug development campaign, certainly not patient cells where we were looking at a patient phenotype. So the question that we were all wondering is will these assays in this platform be statistically robust enough to drive a medicinal chemistry exploration of a drug. And so we needed a test case. So with a serum early translation foreground that was awarded to John Cashman and myself, we set about to reengineer a drug that's used for a cardiac electrophysiology disorder long QT3 and the drug was mixed to a team. We also were grateful for the support of physiologists in New York and in Chicago for the lives of Rocky Cass and Al George. So what is long QT type 3? It's a rare genetic disease that causes ventricular tachycardia and sudden cardiac death, most commonly in teenagers and young adults. Its hallmark is that it has a prolongation of the QT interval on the surface electrocardiogram. Now, a mixility will shorten that QT interval and thereby reduce the risk that the patient will develop a lethal arrhythmia. But the problem is that mixility net slightly higher doses than what's achieved in patients can also induce electrical problems in heart muscle cells. And although this isn't a huge problem clinically because these patients are very well managed, it nonetheless has induced concerns that might induce or aggravate an arrhythmia. So even though it's not such a huge clinical problem, it's a wonderful test case for this platform because we can see the electrophysiological problems of cardiomyocytes quite clearly in these IPS cardiomyocytes assays. So we needed a patient. So Rocky Cass and New York and his clinical collaborators had identified a boy born with a particularly serious form of long QT3. He was actually diagnosed in utero and implanted with a dual chamber ICD that you can see here to control his arrhythmia. You can see the prolongation of the QT interval on the electrocardiogram and he was treated with mixility and responded quite well. So we then made IPS cardiomyocytes from this boy and we wanted to record their electrical activity. And it's much like what is done in clinic with an electrocardiogram. But we do it optically and you can see the beating of the cardiomyocytes and here you can see a normal electrical activity of cardiomyocytes. And here you can see a rhythmic activity where you get a prolongation of the action put to so called action potential and you get these extra spikes known as early after depolarizations. So using this platform and using IPS cardiomyocytes made from the boy, we were able to run through analybaries of structural analogues of mixility and identify what would be the good and the bad determinants in those structures. So we were looking for molecules that were shortened the action potential. But mixility on its own when you give it to high doses will cause prolongation and these after depolarizations. And that's bad. What we were able to do eventually was find four molecules that that would only shorten but even at high concentrations would not prolong. So we produced a safer version of the drug. And this molecule has worked in studies to block the rhythmic caused by long QT3. Now in bold and by that we now set apart a set out to do which is really what I've always wanted to do which is to reengineer on oncology drugs. These are as I said a serious problem about a third of cancer survivors will suffer cardiac problems as a consequence of their treatment. It's not just old cancer drugs but even the new molecularly targeted therapeutics that have this problem. We assembled a large team co-directed by a medicinal chemist Sanjay Mahotra at Stanford and the honest Karakai Kis a stem cell biologist at Stanford. And these are the postdoctoral fellows the trainees who worked on this project. So the drug we focused on was panatmium. It's used to treat chronic myologinus leukemia because it inhibits the oncogene known as BCR able. Now BCR able is in its normal form is inhibited by a relative of panatmium known as amatmium. That is a safe molecule. But unfortunately a large number of patients under have a mutation that arises in the BCR able gene. And that mutation renders the protein insensitive to amatmium in all other first line defense drugs for CML. Panatmium is the only effective drug against this mutation that's been approved. So whereas amatmium is safe as I told you panatmium is cardiotoxic 8% of people have taken it have developed heart failure many more have developed heart disease. But since amatmium is safe we thought the problem with panatmium is an off target effect. So we wanted to remove it. And the IPS platform is ideal for this because we don't need to know the actual reason why the drug is bad. We just need to know that it has bad effects that we can see in the dish. It's difficult to know the exact reason because these molecules target many many proteins in the cell. At least 50 structurally related molecules to the BCR able gene and as many as three or four times as many non-kinase targets. So what we did was we took the structure of panatmium. We started tweaking parts of the compound in order to map the parts of the molecule that are important for its anti-tumor effects and important for the cardiotoxic effects of the drug. And we were guided by the structures of the relatively safe compound amatmium. So we synthesized many analogues in an iterative process and tested them in parallel in an IPS cardiomyocytes in vascular cells which form tubes and in the tumor cells both normal BCR able and mutated BCR able. And the idea was to define the structural determinants for the good and the bad aspects of panatmium. And to cut to the chase I'm going to show you two examples of improved molecules. And in this heat map representation here red is bad and white is safe and these are different indices of cardiotoxicity in the dish. Amatmium is white so safe panatmium is red so bad. And two of these two analogues here you can see are mostly white. And yet when we can see that on the endothelial tumors vascular genesis assay you can see that they do not disrupt the vascular where as panatnib does even at high doses. And yet they continue to block the growth of the tumor cells the smaller number indicates better inhibition of the tumor. And so our new drugs like panatnib will inhibit and even the mutant tumors with the mutant kinase they will also inhibit. So and this works not only in vitro those prior data were in vitro but it also works in vivo if we have tumors human tumors in mice. And by treating with panatnib or with our new drugs we can reduce the tumor burdens substantially. So what I've told you then is that in parallel using cardiomyocytes vascular assays and tumor assays we could engineer a safer version of the CML drug panatnib. We learned that there are different determinants for the good and bad aspects of the molecule and that the new molecules that we produced retain the anti-cancer effect but have decreased cardiotoxic effects in vitro and they have acceptable properties to go into animals and they show anti tumor activity against in xenographed models comparable to panatnib but without the cardiotoxicity. This work as I said has been supported by serum funding specifically for these projects throughout the 10 year history as well as it's been aided by serum training grants to the Sanford Burnham the Scripps Institute the Salk Institute and the University of California at San Diego I directed the training grant to the Sanford Burnham it's also been aided by serum infrastructure grants to the three institutions in San Diego thank you very much. | ↗ |
| 165 | University of Birmingham | Institute of Translational Medicine - University of Birmingham | 1745 | 15 | | 47.9 | | 3:36 | Situated across five floors in the heritage building, within the heart of the Birmingham Health Partners campus, the Institute of Translational Medicine benefits from being in close proximity to a number of its key partners, including the University of Birmingham, Birmingham Women's Hospital and University Hospitals Birmingham NHS Foundation Trust. My name is Francesca Barone, I'm a clinician scientist and my rheumatologist, and my area research is around rheumatic disease. So my group works across two research areas. We work in clinical trials and we work in them mainly in collaboration with pharmaceutical companies, but also we collaborate with companies and with other academics on early research development. And this is mainly through working humans, but also it's an animal work. And for the human work we're very lucky because within the Institute of Translational Medicine we have access to cohorts of patients, so we have the possibility to access to biological material, the patients very kindly donate, as well as clinical data. So these are extremely precious to really dissect different pathogenetic mechanisms in humans. And then we have the possibility to look back at animal work and to dissect some of the mechanisms that we've identified in humans in a more mechanistic way. I hope to develop more our research, more and more into humans, and to really try to understand what is the right drug for the right patients. And this is what we're trying to do here, and our research is going towards the direction, to refine the mechanism of the drugs that we already have, to repurpose drugs that have already been made, and to help in the development of new compounds that will be specialized for specific patients. And that's I think is the core of the precision medicine. The Institute's unique location means that patients and our industrial partners can benefit from the co-location of a number of nationally important buildings, including the Advanced Therapist Facility, the Human Biomaterials Resource Centre, and the West Midlands Academic Health Sciences Network. This co-location fosters and allows research partnerships to flourish, enabling communication and collaboration between different disciplines and expertise, to facilitate the rapid and cost-effective development of new drugs, medical devices and diagnostics. My name is Liam Grover, I'm a professor of Biomaterial Science here at the University of Birmingham. I'm a material scientist by training, but my research really focuses on using materials, both polymers and ceramics in order to try and repair and regenerate parts of the damaged human body. Birmingham Health Partners and the Institute of Translational Medicine have both been incredibly important to my career and to my research. I've always spent time looking at basic scientific phenomena, being able to have my research in the Institute of Translational Medicine, and having links with clinicians and patient groups facilitated by Birmingham Health Partners, have really helped to focus my research so it has the best possible chance of reaching patient benefit. The Institute is a place where scientists, researchers, clinicians and industry partners can come together to translate innovative medical science into tangible patient benefits, rapidly, rigorously and seamlessly. The Institute of Translational Medicine has also been a place where scientists, scientists, scientists, and scientists, can come together to translate innovative medical science into tangible patient benefits, | ↗ |
| 166 | Australian Regenerative Medicine Institute (ARMI) | Australian Regenerative Medicine Institute | 1165 | 13 | | 47.9 | | 6:06 | The Australian Regenerative Medicine Institute investigates the extraordinary capacity of other life forms and how this can be harnessed to develop new approaches to curing human diseases. It is one of the largest institutes of its kind in the world and the only institute in Australia specialising in regeneration and stem cells. Army studies regenerative medicine, which is an amazing science of trying to learn how we repair or replace damage organ as lot tissues. This can occur as a result of an injury or a disease or any aspect of our lives such as old age where tissues wear out and need to be replaced. So it's a potential panacea mechanism for curing and replacing many different tissues during disease. Within our cells we have all the DNA, all the information to make any cell. So all we have to do is re-wake in that information within the cell, add the special factors that enable one tissue to become another, grow that in a dish and put that back in our body. That's the promise or the panacea of regenerative medicine to be able to repair any tissue or any organ from any starting material. Our approach is to try and jump in at the very start of what we think is a growing and spectacular area of medicine and really show leadership in this area. Grow our own talent, invest in the young minds, provide infrastructure that's world-class and really make it a youthful energetic environment where innovation is the buzzword and we make the best of trying to take this new technology and push it and pull it in any way we can to create new therapies. Every year, 1000 Australians are diagnosed with multiple sclerosis, 50,000 Australians suffer a stroke. Currently over 3.3 million Australians have arthritis, 4.2 million are affected by heart disease. One in 10 Australians over 65 have dementia. Research and Army are structured along four integrated discovery pipelines, heart and muscle development and regeneration, immunity and regeneration, stem cells and regeneration, neural regeneration. I'm group leader of the born group at the Australian Regenerative Medicine Institute and I focus on neurobiology, understanding the mechanisms of how the brain develops and how this contributes to brain disorders and diseases. So stroke is the second leading cause of death and disabling in Australia yet there's no treatment essentially to protect the brain. All that's available is a drug that you need to administer within three hours at an unblocked so-cloth. We're looking to find that therapeutic that can protect the brain cells and enable a person to essentially get up and walk out of hospital again. One way we'll hope to find is the cause for heart disease and babies that are born with heart defect. So we use a computer programming to predict in our DNA which changes my cause heart disease. My research field is quite unique because it combines computing and biology. It's quite challenging because you need to have a background in both fields. It's called bioinformatics. So I really encourage students to tackle multidisciplinary field because this is the future. Being able to combine big data analysis and biology. Once we've had a suspicion using our computer programs that certain changes in our DNA might cause heart disease, what we do is we use fish to validate our experiments. Because fish hearts are very similar to human heart except that they are outside so you can basically just look down the microscope and find changes that are triggered by the changes in the DNA. I'm the leader of the Martino group and basically we try to understand why we cannot regenerate most of our tissues. And we believe that it's because the immune system is very important in the healing process. So basically we have shown that we can promote regeneration just by modulating the immune system. For example we can close chronic wounds in diabetic models or we can even regenerate very large bond effects that cannot regenerate normal. Army has developed industry and research partnerships locally and across the globe creating opportunities for exchange of faculty, post graduate students and research staff. In a very few years, Army has become one of the largest regenerative medicine research institutes in the world and it is the only regenerative research institute in Australia. So I think we've been off to a pretty good start but we have the opportunity I think to double the research institute over the next five to ten years. An opportunity to add more researchers to go into more research in greater depth and I think that's a great opportunity for us. And Army is a magnificent center. We've seen it grow over the years, got fantastic people leading in many areas of research and publication around the world and it's this drive to come up with new solutions, new regenerative medicine solutions which may well provide the answer to many of the big disease challenges that we've got in Australia and across the world. More investment really means more young bright minds working on these incredible problems. Being able to use this new technology in this new approach in ways we never dreamed of. Curing diseases we've never ever dreamt of being able to try and tackle before and really trying to push the envelope on how regenerative medicine can be used to treat the human condition and the things that ILS. | ↗ |
| 167 | Mayo Clinic | Mayo Clinic Study Shows Induced Pluripotent Stem Cells Repair Heart | 3806 | 11 | | 47.6 | | 1:44 | This technology has been used in proof of principal concepts for other diseases such as Parkinson's and sickle selenemia. But this is the first study that has demonstrated that these cells have the unique capacity to repair and regenerate the heart after a mild cartiline fraction, where there is severe damage to multiple liniages throughout the heart. IPS cells have a unique ability and that they can recapitulate the unique features of embryonic stem cells that being said they are able to give rise to literally all tissues of the developing embryo and adult body. This feature has previously been only possible with embryonic stem cells and now with this technology we can recapitulate that ability using ordinary cells to start with and reprogram them back to their embryological origin. The word is pluripotent autologous stem cells. That means that these cells have all the potential of embryonic tissue or embryonic stem cells but they are derived or they come from your own body so they are autologous. This is a unique ability that isn't possible with any other cell type and what it allows us to envision and allows us to do today in experimental studies is to use the cell from an adult, create the stem cell and transplant that back into the same individual. This allows the body to recognize that it is self tissue and not rejected as foreign tissue. | ↗ |
| 168 | Stanford Cardiovascular Institute | "Cardiac Cellular Reprogramming: Doing the Unthinkable" - Todd K. Rose... | 610 | 9 | | 47.6 | | 52:32 | Stanford University so it's my real honor to introduce my close friend dr. Todd Rosengarten dr. Rosengard did his undergraduate medical school with honors at Northwestern University and did his general surgery training back when we had general surgery training as part of our pathway did this at NYU and then he went up to Cornell in New York City to do his cardiothoracic surgery training and during that time he became involved with a very famous research scientist Ron crystal and the two of them actually pioneered a lot of the work in cardiac gene therapy and the world's first the u.s. is first trial looking at veg F gene therapy in the heart in a clinical trial for myocardial ischemia he's gone on to pioneer several new things in cardiac regenerative therapies and not only has he continued to be active in the surgical arena but has maintained a very active clinical practice in valve surgery and coronary surgery despite being a chair at two programs dr. Rosengard became the chair of the Department of Surgery at Stony Brook and then most recently became the DeBakey chair of surgery in Houston at the Baylor College of Medicine and among some of the people that he has the privilege of working with on a daily basis include names for those of you in cardiac surgery familiar with these names people like Denton Cooley and bud Frazer and Joe coselli and a variety of other luminaries who have published really a lot of the history and the development of cardiac surgery these are the people that dr. Rosen Gard has the opportunity to work with on a daily basis now so dr. Rosen Gard also has had a very viable and continuously funded research laboratory funded from the NIH with a tremendous publication track record studying gene therapy and cellular reprogramming and other regenerative therapies and is here today at our invitation to educate us on novel reprogramming technologies and trying to do the unthinkable thanks Johanna while we're getting us started up first of all my thanks to all Joe and and Joe and a great old friend and a great new friend and it truly is a pleasure I don't need to of course tell anyone here how significant and memorable Stanford is but by coincidence I will mention that one of my other side jobs is editing one of the cardiac surgery journals Seminoles own thoracic and cardiovascular and we recently ran a special issue on great institutions in cardiothoracic surgery and the the very first article was Stanford a hundred years of history here that Jo Jo Lou surgeon contributed and of course truly a remarkable place that we all from the outside you lose perspective on on who you are and what you're doing when you're at a place for very long but of course needless to say stamp Stanford is a a very very special place in all of our consideration so I'm going to talk to you today a bit of science but perhaps equally importantly especially for the younger residents and our PhDs and our scientists in the room the concept of thinking the unthinkable and really most of what I'm going to talk about about my 30-year journey in terms of cardiovascular medicine and science and discovery is really unthinkable and as we've heard this morning most of what we're talking about today if you talk to some of the older people in the room would really be close to heresy to suggest for example that you could grow new blood vessels or let alone take a fibroblast and turn it into a cardio myocyte you would literally have to be committed you would be banned from future science and the like but the again the theme of what I'm hopefully will convey again especially to the younger scientists is if the data are there and you believe in what you're doing think the unthinkable and go for it and again I think a lot of what has been ah so wonderful and I'm so grateful about it now my career is having had the opportunity to do that so the theme of what I'd like to talk about today is the treatment of a heart failure as many of you know this is remains a very very significant problem in a merican medicine five million Americans have heart failure current medical and surgical therapies are still associated very high mortality limited of applicability as we'll talk about 300,000 patients or individuals annually required transplant or VADs but less than 5,000 transplants or VADs are performed annually of course Stanford is a truly the epicenter and the home of certainly heart transplants and of course the VAD program here is a second to none so in many ways there are probably at least a million individuals in the United States annually who are candidates for something other than having their heart cut out heresy to say it here but it's true or having a machine put in their chest to take over heart function wouldn't be it nice if there was a biologic way of repairing someone's own heart so we didn't have to undergo such extreme surgical procedures again hard to believe a surgeon would be saying those things but it's true again as I mentioned even under the best of circumstances Marc Marc slaughters data from New England Journal in 2009 there's still a 20 or 30 percent two or three year mortality associated with even even the best of mechanical circulatory support devices and then again of course I'm having to do heart transplant is is not a trivial undertaking recent story as we're going to talk about we're getting ready to undergo begin a angio genic gene therapy trial and I was sitting on the medical review board over Texas Heart just a few months ago there's a patient with end-stage angina and literally had failed all medical therapy no bypass no angioplasty operation and they were literally talking about this patient who said we're going to do a heart transplant as nothing left to offer this patient normal ejection fraction just advanced engine oh yeah sheepishly raised my hands and fretted in the room with all these heart transplant surgeons I said before you cut this patient's heart out maybe we can inject some genes into the patient's heart and let him grow his own bypasses and by the end of the meeting I had about seven cardiologists lined up wanting to enroll patients in the trial clearly underlying the fact that there's a tremendous need for what not needs to come next other than such aggressive surgical therapies so I'm going to talk about this morning and I will get to this towards the towards the end is something very different and this will be a little heretical then what is customarily thought of the cell therapy for treating advanced heart disease most of the time an important that we're clear on this definition and depicted on the top right is a obviously a cross section of this experimental animal of an infarction the area of a thin tissue over here most of the time when we're talking about stem-cell therapy and again I'm probably gonna offend a number of people in this room right now what we're really talking about is depicted over here this is again an experimental model and we're taking a large area of infarction and we're judging a bunch of exogenous cells stem cells mesenchymal stem cells embryonic stem cells iPS cells even taboo area to a be critical of and what we're doing is something that ends up looking like this and if you talk to most stem cell scientists they will say yeah that's what it looks like so you have this giant area c of fibrosis and you have islands of stem cells working there and then these scientists say well this is great this improves heart function dramatically and I and others will argue and the clinical trials will support it really does not makes much sense that these islands and stem cells sitting in a sea of fibrosis are really impacting global heart function so we'll get back to that we're going to talk about this after afternoon is incite to sell you're reprogramming this sort of crazy idea that you can actually take some of these fibroblasts in the area of my myocardial infarction actually convert them by direct reprogramming back into a cardio myocyte phenotype and thereby improve function so let me put it that aside for a minute and go back about 30 years it's hard for me personally to believe that I'm telling a story that's thirty years old but it does happen to all of us and I guess I'm there and talk about the problem of advanced coronary artery disease so again as with heart failure still a very significant problem despite the fact that we do over a million a coronary stents almost half a million coronary bypass procedures annually but the secret truth be told is that about in half the cases we don't completely revascularize a provide blood flow to the entire myocardium that said risk because of ischemia or poor blood flow because of coronary disease in fact through a number of large studies that have just been done in the last few years syntax freedom among others we now know and we didn't know this up until about five or ten years ago that if you don't completely revascularize myocardium the mortality risk is about double compared to patients that are normal or completely revascularize so again a tremendous opportunity for something other than bypass or and your power angioplasty to improve things so we are going to talk about having the heart grow its own bypass is biologic bypass or angiogenesis and that's going to take care of everything so let me go back thirty years I was a resident working it down at the NIH my mentor Wayne ice and was the chair of us or cardiac surgery at Cornell said I didn't know what to study or what to do research on it showed me two angiograms one of the patient who had a totally occluded a coronary artery the other had grown would appear to be collaterals they said go and figure out how to grow those collaterals i saluted dr. Reisen and i marched off to the nih and you come back when I have it figured out of course that did not happen and back in the 1980s the only thing we knew about any of this this is truth was that work by Tom meshach and others who were just beginning this is true to learn how to grow endothelial cells and culture this is 1980s that's when this whole story what Tommy Jack realized and showed in this paper in science in 1982 is that if you would drew a culture medium support protein called at a time heparin mind in growth factor-1 or acidic FTF today you grew these structures in vitro and cell culture that sort of look like capillaries that was it that was the entire initial field of angiogenesis these funny things in cell culture that look like capillaries we were talking this morning with dr. nan and we were saying that you know well how do you do these things and you need to have the proper combination of growth factors it's got to be in the right sequence and in reality if we ever tried to grow a blood vessel and come together with all of the different structures and molecules and cytokines and integrins and the like to make it all happen we all would have quit a long time ago but being dumb surgeons we didn't know what we didn't know and we just said we can take ng jobs such as fgf or in our area of interest veg F and buy some very fortuitous a pathway if you administer those exogenous antigens the entire angio genic cascade will get stimulated and that's exactly what happened we became interested within vascular endothelial growth factor for a number of reasons now none less than there was a very potent angiogenic mediator as I think everyone knows it comes in three different isoforms 121 165 and 189 and essentially all of the work that was done involved one of those isoforms we'll get back to that in a minute as a Joey mention I would had been doing my work you know angio genic therapy collaborations and relationships which you all here at Stanford so fortunate to have or critical I think to a scientific success and I was fortunate to begin a collaboration at Cornell with Ron crystal who is Joe mentioned had been sort of the innovative one of the early innovators and pioneers of gene therapy and sort of like Reese's peanut butter cups when you have the right combination of two things of nothing to do with each other my interest in angiogenesis coincided with our lawns interest in gene therapy and I said I've got this vascular endothelial growth factor I don't know what to do with it and Ron said I've got this adenovirus vector and I don't know what to do with that well so why don't we put them together and we didn't end up with Reese's Peanut Butter Cup but we ended up with a nice collaborative research so ad virus and despite speculation to the other wise is a tremendously effective delivering a fairly large packages of cDNA for to induce transgene upregulation again in our case we are interested in veg F is in particular very efficient at getting into cardiomyocytes ideal for cardiac gene therapy applications and importantly on this is something that is miss no or misunderstood about adenovirus is it is a short-term expression vector last about three to seven days it remains epic chromosomal in a location thereby preventing a mutagenesis and it down regulates not through necessarily through inflammation but probably by means that we don't completely understand so again very simply I think everyone knows that the concept is really just regional pharmacotherapy we are repackaged adenovirus with the aussie DNA in this case for veg F 121 we are delivered to the myocardium in order to turn on a local of fiber cardio myocyte induction of a veg F the concept is the gene therapy as we envisioned it was just a local drug delivery therapy no more no less in order to deliver veg f ng Jen in order to cause new blood vessel growth to revascularize scar my aquarium that could not be treated by standard therapies well back when we started no one knew whether this would work went to a small animal model with AD Jeff's 121 and his concede on the right be able to induce profound angiogenic effect in a rat retroperitoneal fat pad we found very early on that this was just pharmacokinetics you give more veg F or adenovirus you get more of an effect this is a standard pharmacokinetic therapy I mention this because people forgot that this was just a drug and they thought it had magical properties and what ended up happening were applications that were inappropriate and unfortunately it caused the entire field to crash and ended up setting the program back for about 10 or 15 years because people forgot these basics again importantly adenovirus works very very well because it ended up that we just needed 10 days or so of trans veg F trans gene expect expression to have an effect conversely if you used a chronic expression vector like adeno-associated no associated virus as shown in this paper by Lee you ended up with hemangiomas more trans gene more veg F deleterious effects limited expression and preparin as we later showed solid efficacy of all the slides that are and data that we published the one that or we produce the one that we actually never even published is this slide right here probably more important than any work that we did probably cost the gene therapy industry hundreds of millions of dollars in false starts and lack of success including companies so that presumably is a bright as a Genentech and it is all all that that is depicted right here this is a very very simple study anyone's child to grandchild in this room could probably do this study in very early on in gene therapy days we asked a simple question what's the best way to deliver adenovirus you get the trans gene into the heart and get in effect if you injected intravenously should we inject it in the coronaries as she injected directly in the myocardium simple study here that here's the results and if very clear to see you have about a 1 or 2 log fold increase in local myocardial expression we use a beta galactosidase marketing if we went with intra myocardial delivery versus intra coronary delivery or intrude intravascular delivery much more efficacious to go with direct intra myocardial delivery we'll come back to that point in a few minutes so we had our vector adenovirus short term expression that's all you needed we didn't need to form hemangiomas we had our transgene veg F we had shown in vitro and in small animal model was effective went to a large animal study and this was sort of our Eureka moment back in the mid 1990s we took Pig standard model we put a circumflex amyloid constrictor around it tied off the coronary artery just as if you were having a heart attack we treated the animals either with the null virus without veg F or virus with veg F 1:21 and as exactly as we saw in human angiograms we saw that we were able to grow a plexus of collaterals and literally reconstitute the circumflex coronary artery just as if as a surgeon I was doing a bypass operation on the basis of this large animal data we went to FDA in the early 1990s we said we wanted to treat patients with end-stage coronary disease we're just going to take this syringe injects this solution to the area of an farc Shen grow new blood vessels and the FDA said you have to be kidding that's the craziest thing we've ever heard of we're not gonna let you do it and I don't care what kind of data you have this is very bizarre and you all should leave and we really were up against a complete dead stop all we wanted to do is take a tuberculoma syringe inject 1/10 of a CC and of this veg F solution into the heart and we really didn't know what to do so for those of you who have been around for a while this around this time in the mid nineteen ninety there was a technique called TMR trans myocardial laser revascularization and some crazy of physicians and surgeons had the idea that if you took a laser beam and drilled a series of holes in the myocardium you could reproduce a reptile heart and the heart would profuse itself directly from the chamber well that for some bizarre reason had already gotten FDA approval but the key point of the story was that we happen to have a video from the local Channel 2 News in New York of Craig Smith and well-known surgeon using the TMR laser beam to drill those holes in the heart with this fda-approved trial but more interesting the local channel 2 reporter thought that it would be dramatic if he took the same laser beam that they were drilling holes in the patient's hearts and took a 2x4 and drill took the laser and drilled holes to the 2x4 so we're at lunch break at the FDA and really we're about ready to go home and I said Ron you know Ron crystal my partner Mabley she showed the videotape but the 2x4 that's a little funky you know I don't know and I said let's give it a shot so we put the video tape in I was back in the days when I still videotape FDA panel 20 people in the room turn on the video laser goes on on the video two-by-four smoke flames fire everything and we said you guys just to prove this last year all we want to do is inject the solution in the heart we got approval and now we're off to our clinical trial great science at work absolutely true story so the first trial was done in December of a 97 at Cornell as Joe mentioned first time anyone at least in the United States had ever inject a virus into the heart a little bit scary we found a lawyer from Westchester to be our first subject and we went we went on and did a series of patients literally just injecting a grid of a sort of gold elack's a little red riding-hood with a breadcrumbs in order to inject it really did not know much of what we were doing our most famous patient was columnist for time Meaghan magazine named Lance Morrow Oh get that that back to that in a second but after a phase one dated we had encouraging a preliminary data our patients seem to be feeling better there's a lot of controversy that this might be a placebo effect but we continued on and this went on to a faith to study in Canada we were not involved in this basically looked at an FDA approval endpoint which is time to one millimeter ST depression and what was shown here with a very small and 26 patients looking out to 26 weeks after therapy patients either getting the adenovirus with veg F or a medical control group - statistically significant improvement in evidence of EKG changes not just angina with this a very very small group so pretty encouraging look pretty good and in fact in that study there was one patient who died for unrelated reasons they're able to get an autopsy this is a alkaline phosphatase stain that's brown from blood vessel this is an untreated myocardium you can see a couple of blood vessels this is treated myocardium pretty impressive looks like where the bed jeff was delivered significant increase in angiogenesis and Vascular ization but then as I mentioned and go back to that pharmacokinetic study that I showed you early on interesting thing happened we were going but direct myocardial injection again this is what our data showed us we found it that we and others who had used direct my connection found that there was appeared to be a significant improvement in terms of exercise treadmill based upon EKGs but then there were a number of trials the vive trial again this was a Genentech trial Nicola Napoleon for our brilliant scientist Chiron to study with basic fgf and in these placebo controlled trials again these were in Turkana a so they could use a placebo no significant improvement in terms of exercise treadmill everyone said you see those scientists those guys at Cornell were wrong they were oh this was all placebo effect because it was Rep myocardial administration everyone wanted to feel better when you did the good placebo-controlled intra coronary trials no effect and therefore placebo controlled trials are always better than open label and therefore field doesn't work we of course argued that there was a hundred fold decreased uptake into my car diem with intra coronary fell on deaf ears this is all sort of written off as a placebo effect and then a very significant thing happened again let me go back to an anecdote and admittedly this is an anecdote our most famous patient was a columnist for Time magazine Lance Morrow who had done a story about gene therapy again this is in the late 1990s and said then came back a few weeks later and said you know I did the story but I'm actually need to be in your trial I've had a couple of heart attacks that can barely get across the room anymore and he subsequently went wrote a trial about going back and playing squash and doing doing great in fact we stay in touch to him to this day ten ten or fifteen years later and continues to do well interestingly so again looking pretty good gene therapy seems to be working and in a tremendously a tragic event happen again probably everyone in this room will recall back in the late 1990s a young man named Jesse Gail singer got about a thousand fold excess dose of an adenovirus he was being treated for a benign inborn an inborn error of metabolism of onething trans carboxyl carboxylase was not affecting him at the time and he died from inflammatory effects of a thousandfold XS dose of adenovirus delivered intravenously and basically this put a hold on all gene therapy studies in the United States and FDA moratorium and it literally took about ten or fifteen years for the field to recover again very famous scientist Jim Wilson and his team at Penn had been doing great work in the field and have clearly made an error in terms of administration so then an interest same thing happened we as many others walked away from the field Joe Joe loo surgeon had been involved as well and we all really went on to other things stem cells in particular I at a time had lost left Cornell gone out to a northwestern and then came back to New York about ten years later interesting things started happen one after another a number of these patients who had been in the original gene therapy trial started calling say hey doctor Rosengard I hear you back in town just wanted to let you know I'm feeling pretty good I don't have anymore angina and glad you back in New York great that's really nice second time happened third time happened about the fourth time one of these patients call and I said to myself and sort of almost say that like you know I thought you'd be dead by now it's you know 15 15 years later and you had end-stage Carter just peace you tell me your engine of free and uh you know fortuitous Ness is only useful unless you do something about and in speaking to Ron crystal he said we really need to follow up on this we track down all of our patients about 32 who had received gene veg F in our trial and interestingly just as a data point what we found is that the survival of these patients compared to a TMR control group and TMR again was I got no statistics here but seem to be better certainly ten-year median survival much better than we would have thought in this n stage coronary disease patient and perhaps more interestingly you can think back to the angiogram of the pig here's an angiogram ten years after veg F therapy and one of the patients and we had about three or four of patients with similar angiograms you can see that again that plexus of blood vessels this was exactly where had given our veg F therapy persistent 10 or 15 years later so we got to thinking about it and we decided maybe we need to go back and pick up the work where we left off don't isn't it isn't it the right thing to do and in classic sort of Silicon Valley star is telling the story to a friend actually a gentleman Hudson news if you in the news in the airport and he said you know this is you really are should be ashamed a self Tod you really should continue this work and I said oh you don't understand it's complicated and he persisted and persisted gays gave us some seed funding and we went back to the laboratory and said if we had to do it over again how would we do it differently and better and so one of the parts of the veg F story again as everyone knows is that veg F just doesn't come just as a single polypeptide it actually under those post post transcriptional splicing and ends up is three different major isoforms 121 165 189 again is anyone in the field knows they have different biological functions they do things slightly differently in terms of relevant receptors heparin binding and the like and he said well you know if Mother Nature has three isoforms maybe just delivering one isoform like 121 and 165 how the trials were done is is not the most effective way and our on crystal and his team who are really truly experts and quite innovative created this genomic veg F which we called veg F all that actually expressed all three isoforms so seen here on this Western over here and all three about 2 to 2 to 1 121 165 189 I went back to the laboratory looked at a hind limb ischaemia model and what we found basically is that the veg F all was approximately a hundredfold more potent than veg F 121 which was encouraging in terms of a new clinical trial in fact Ron went one step further looked at alternative alterations of the of the proportions of 121 165 189 and we created a veg F all six a plus this has to do with the expression of the six a.m. exon and what he found long story short is that veg f68 plus is just as potent as veg F all but when you look at things like pulmonary edema and even immortality' the Jeff 6/8 plus was safer likely because it was less veg f 121 even though we had no trouble in our clinical trials but because of its ability and induced vascular permeability and the like so we went back to the FDA we saw the TMR tape in our back pocket but at this point interestingly when we went to FDA they had no concerns about safety which is very very significant considering how far the gene therapy field had come but when we proposed to them and received approval from the NIH for comment visor e committee as we said look the biggest problem with the veg F trials back in the 90s was that the ones that worked such as ours we argued um didn't have a placebo control and so NIH and FDA said well not only do we think having a placebo control veg F trial is an interesting idea we actually think it's the most ethical thing to do and the amount NIH recombinant Advisory Committee is depicted here actually approved a clinical trial we had randomized patients three two one two with end-stage coronary disease either get add veg F all or actually get an ADD null vector that might have some inflammatory effects but it would clearly was a negative control and then I had to prove that unanimously eighteen to zero and FDA although they want us to stop in Part A which is the open label trial will hopefully be supportive as well and we're about ready to undergo that trial which we'll look again at the primary endpoint at time to one millimeter ST depression other standard secondary endpoints interestingly we're going to include cardiac pet which we think will be more sensitive and we'll be conducting this study in New York at Cornell with Ron Ron Crist on this group and that the Texas Medical Center which everything's bigger in Texas so it's the world's largest Medical Center and obviously a hopefully a very suitable place to recruit patience so that's where that story leaves off and now let me go back to a little bit of sort of unthinkable science so I think part one is the unthinkable part of what you can do with some some persistence and belief and the basics of the science let me go back and talk again about what I think from a scientific standpoint is many in this room know and have been working on something even more unthinkable which is taking one cell type by direct reprogramming in turn converting into another obviously this field all came about because a Yamanaka is work with the IPS generation is depicted in the box but the problem is I alluded to earlier is that with all stem cells exogenously delivered the problem is how to get past integration into the host genome host milieu the whole host of myocardial matrix in a way that's clinically relevant so deep extra warszawa i've just up the road at UCSF really was on the pioneer amongst other as Eric Olson in taking Yamanaka his work and taking it one step further and basically he said well if you can take an adult somatic stem somatic cell use ox ox klf4 to induce IPS cells perhaps you could take another combination of transcription factors and directly reprogram without going through an IPS stage from one adult somatic cell type into another and what servoz Tova showed in his work that came out about now I think four years ago was that you could take a gatah form F 2 C 2 X and TB x 5f to say and TB x5 which are associated with cardiac differentiation in the embryo logic state using a lentivirus and directly trans trans differentiate fibroblasts and to induce cardiomyocytes and service are in a very elegant papered seem to demonstrate this we quite frankly couldn't believe it you know never having been taught anything like this was possible only repeated on the service of his studies and in fact duplicated what he saw so it's depicted here if you start with cardiac fiberglass in vitro administered GMT you could actually up regulate cardiac specific markers in this case looking at cardiac troponin T and GMT treated fibroblasts versus control fibroblast we can see market a dramatic staining for cardiac troponin T if you look at other markets such as myosin heavy chain 7 or alpha sarcomere actin similarly up regulation of these markers and in fact survived among others went on to show that in vitro you could actually induce contractile cells this creates a sort of - to me is a is a cardiac surgeon in my day job an intriguing possibility which is instead of administering exogenous stem cells and trying to get them integrate into the host myocardium perhaps you could again take these transcription factors just an aliquot of solution injected into a large area of scar and actually trans differentiate scarifier of last insight - so they're already integrated into the host myocardial architecture to induce cardiomyocytes and therefore regenerate my accordion from areas of scar tissue so again very very important to think about the basics and one of the first questions we asked which sort of befuddled us and really hard to believe we thought we were missing something is that the I don't understand question and against of thinking of this as a cross-section of heart infarct in myocardial here why did the heart become fibrotic it was there it was because it was an inadequate blood supply all of those residents cardiomyocytes died became replaced by fiberglass so why if they're still ischemia if we injected cells into the scar tissue would you get anything other than persistent scar and they injected cells undergo the same fate as the resident cells which would to be to undergo apoptosis or otherwise die in fact work by Maria McGovern showed exactly that if you inject exogenous cells about 98% of them are dead within a couple of days either because of poor delivery or again ischemic loss so we did a series of experiments this again is about five or ten years ago we were still at this time looking at stem-cell delivery and we said okay well since we're angiogenic people everything if you have a hammer everything looks like a nail why don't we create a scar let's previs karai's the scar with veg F so we're essentially fertilizing the soil before we deliver ourselves and we speculate that if you pre vascular eyes provide a blood supply to that scar tissue then inject those cells you'll have a better result than if you just try to get those cells to stay alive in this hostile ischemic milieu and we did some experiments early on and we treat animals with veg F and nothing sells in nothing or a combination of pre vascular ization we actually put the rats on a treadmill this is clearly not a Stanford student in the front and what we showed is that with the pre vascular ization we couldn't significantly enhance exercise treadmill results and that became our standard model of pre vascular ization so come back to that in terms of further studies so if we're going to do insight to celery reprogram again again the same model pre-vet and induce like infarction by coronary ligation pre vascularized wait three weeks which is how long we knew it took for the new blood vessels to grow and then either administer get gado-gado GMT got a form F to CT bx5 or a control vector and then wait look four weeks and look at results and much is savasana and others showed quite dramatically and a tremendous surprise to us if you look at histology this is control bland infarction coincidentally or not and the data is the data and the treated animals we see these distant islands and strands of myosin heavy chain positive staining cardiac myocytes being induced cardiomyocytes and natives couldn't tell for sure looking at trichrome staining for fibrosis control not only is it tremendous thinning actually of aneurysm formation compared to an almost normal-looking cross-section of treated myocardium and then is shown looking at ejection fraction by echocardiography again what appeared to be dramatic improvement and function again looking at is statistically looking at myocyte density statistically significant improvement and induced cardiomyocytes statistically significant improvement in the amount of fibrosis and finally looking at ejection fraction veg F pretreatment plus GMT statistically significant improving an injection fraction at dramatic twenty twenty thirty percent levels with this reprogramming vs. control treated rats interestingly if we were using three vectors and this is sort of confirmation of what we had done previously the GMT we're all being administered with three separate lentivirus vectors if we combine those into a single triplet vector so each cell is not needing to be exposed to three different trans genes but all in one vector at the same time we showed a significant improvement in function this at this point it was a up to a 40% improvement ejection faction using this triplet vector again very very encouraging a data suggests that you could actually reprogram hearts by this technique most recently this is a material that will hopefully be a presenting this year going back to or you originally talked about all of this worked involve Lenti virus or retrovirus chronic expression vectors but most recently with now reduplicated these efforts and show that we can actually use an acute expression adenovirus vector to also induce improvement in a heart function so perhaps most dramatically olson and others have most recently shown that even though we're getting these very very encouraging results in lower order animals such as mouse and rats when you get to higher order animals such as humans the all of the data suggests that ourselves a much more resistant to reprogramming probably because of epigenetic stabilization compared to lower order animals and in fact it adding GMT to human cells in particular would not induce reprogramming and Olson and others have now shown that only by adding multiple of other factors such as hand to Maya carton on top of the GMT could you induce the reprogramming of cells such as human cells so obviously - I study these things we need to needed a good surrogate and most recently and I don't know if this will play but we've actually now been able to go to in vitro Pig cells and as you can see here we've been able to induce beating Pig induced cardiomyocytes these were originally fibroblasts that are now beating based upon administration of reprogramming transcription factors so they're our most latest work and the theme of this could potentially be we could be tadpoles if you'd like is how do we get past this problem of anti plasticity of human cells versus Road in cells and probably and this is an area of a new investigation there's a lot going on in human cells it's not present and rodent cells that are preventing our gene gene act genes from being activated into factors are probably very significant in this that we found out through IPS studies is p53 and p63 so obviously everyone knows that p53 mutations and one of the primary causes of a hunka janessa t but we actually believe we have found that we could actually turn that around and look at it from a therapeutic standpoint and not focusing so much on p53 but it's cousin in the p53 family p63 as much as this when these are down regulated they promote mutations and oncogenesis 'ti essentially by allowing increased cell plasticity we could take that to our advantage in terms of reprogramming and we most recently have shown that if we down regulate p63 this anti plasticity gene we could significantly increase as shown down here our ability to reprogram fibreglass into cardiomyocytes as evidenced by nearly a sevenfold increase in CT expression in these cells so very early work very exciting essentially suggests that there are a lot of ways to enhance the plasticity of mature somatic cells such as fibroblasts for the purposes of reprogramming as suggested by these data so in conclusion really on what has been a incredible hard to believe 30 year journey I think we are back in the gene therapy arena we will be seeing more and more in terms of clinical applications including angiogenic gene therapy trial that we look forward to a beginning this year we think that I'm going back to the basics and the concept of pre-treating the infarcted myocardium is incredibly important in terms of making sure you have essentially all of the principles aligned in terms of ideal opportunities for enhancing these therapies and finally although formidable variant remain and work at places like Stanford and others will inevitably and undoubtedly lead to advances in the field we think that there's an entirely new chapter to be written in the next five to ten years terms are using a cardiac cellular reprogramming to completely rewrite how we treat patients with advanced heart disease so again regenerative therapy is a truly a new paradigm for treatment of heart disease we think it is something that will be as seeing increasingly greatly and I thank you for your time and attention thank you so thank you very much for that amazing lecture showing us both some history and really what the future is going to be I think we have just a couple moments for a few questions from the audience Phil yank yeah so as we're talking our thanks Phil as we were talking earlier I think what's most interesting so this is kind of data you see from your own laboratory I said well what did we do wrong you can't really believe it and one thing that's heartening sort of speaking that is now about four or five groups Olson's Rostova some of Deepak's disciples have now gone back to japan we're all seeing the same thing so the fun part is I think we've got the end point which is there truly is 20 or 30% to give us statistically significant proven and function which of course is a clinically relevant endpoint we actually now need to take a step back and really really understand what's happening and I think it would be foolhardy for us to say we're creating these cells and that's the story there are clearly other things going on for example there's probably an anti fibrotic effect it's potentially gatah for playing a role in that there's probably other things going on and we just don't understand and for anyone in this room who's looking for something to study I think especially because we know that it we don't know but we seem to have evidence that it works it's just a fertile for a lot portunity to go back and start understanding mechanisms that's obviously what we're spending a lot of time doing the efficient so the other thing I would say that again is fascinating this field is it it appears and we're going to talk about this morning that the efficiency in vivo um sort of fortuitously is actually better than the efficiency in vitro and we see that a little bit one of the magic tricks that I didn't fully explain was that on those beating pink cells they only work if you have coal culture with cardiomyocytes so then again we feel comfortable that these truly are the pig fibroblasts but yet you need the co culture and again Deepak has shown that too this is clearly in vivo insight to crosstalk communication hand-wave and we don't understand it that is important to making this more successful more efficient in vivo so wide-open opportunity to try to figure this out yeah so and again I was talking to Joe about this earlier we believe in ad now and one of our greatest frustration we believe in it not just intellectually or emotionally because we've used it clinically we intensely looked at safety parameters we've never had safety parameters issues we know that it works for as long as we need it to we don't want to have chronic expression with AAV and one of the challenges again is one of the sort of the fascinating things about how the feel that works is that is that the science and the sort of you know feeling on the street just don't line up and one of our challenges all of us and again Stanford of course is one of the great incubators of translational science is to convince and explain to the lay public why their impressions are not scientifically based and much more than a science communicating fault false miss properly communicating people away from false impressions that I'd know is bad are one of the greatest challenges we face much more so than just the science so yeah we are using ad know we think it's the perfect vector for this utilization and interestingly when we went to FDA and NIH and said we want to use ad now there's no issue there completely supportive they actually not even asking us to do all the safety studies that we did in our original phase one studies and again for those who actually they knew we had the tape right very interesting paradox that goes beyond what you do in the laboratory one last question whenever gene therapy comes up I always ask what the status of for cardiac gene therapy what the status or theoretical potential of coxsackievirus would be as a vector you stumped me can't answer good are you gonna tell me no I just think I think of the natural disease process in the relationship of Coxsackie to myocarditis I mean it's a vector that's in nature designed to get into cardiomyocytes and no one has really harnessed it and it's just something that's maybe it's too dangerous to do again anyway thank you very much for that wonderful talk and I would invite everyone to join us in the photo Stanford University | ↗ |
| 169 | OrthoBiologics Associates | Say Goodbye to Surgery: Try Regenerative Medicine First #regenerativem... | 2222 | 9 | | 47.4 | | 0:30 | Any problem with a joint, whether it's traumatic in onset or chronic in nature, if it damages specific tissue, it's always going to progress to end state because that tissue can't heal. So we typically only have drugs and surgery as two primary tools, regenerative medicine fills that gap and it allows us to heal things. Having the capacity to heal damaged tissue is really an amazing thing in helping people recover. That's really the key. | ↗ |
| 170 | Temerty Medicine | Translational Research Program | 4931 | | | 47.2 | | 5:08 | Hello, I'm joined today by Joseph Ferenbach and Stuart Berger, who are here today to talk about a new program that's been introduced by the Institute of Medical Sciences at the University of Toronto, known as the Translational Research Program. Gentlemen, good afternoon. Can you tell us a little bit about why the TRP program is needed right now? Well, let me start by explaining what translational research is. So translational research really describes the process by which basic discoveries, clinical insights, even health policy initiatives are actually taken from laboratories from the clinic and brought into the real world where they can have impact. And there's a huge unmet need for translational research because I think everybody understands that our healthcare system is really under strain. And as our aging population grows, you know, we would be faced with all kinds of health challenges. And there's a consensus that simply doing the same thing over or better is not going to be the answer. Our system needs innovation. Our program is really designed to teach students to be facilitators of those innovative opportunities that will transform healthcare. So Joseph, how does the program make that happen and why is this a place to make it happen? Well, the central aspect of the program is the capstone project. So we don't just sit students in a classroom and say, here's your textbook, SIA. Here's your lecture, you know, write an exam. This program is fundamentally learning by doing. So students engage with faculty and mentors in a very flexible environment where they go out, they identify needs, ingenuity gaps, things that they look around and they see are missing or have potential for improvement. And then they come back and they say, okay, what can we do to improve this? What can we do? What can we design to solve this problem? And the capstone project becomes this vehicle whereby they build networks. They go out and understand the landscape of where things are, what's happening. They build relationships. They put in creativity and problem solving skills in order to plan a project, in order to meet milestones, work with researchers, faculty and other students to then execute and then evaluate what it is they get. Will it help? What could it do? Where can they take the next steps so that really this bit about translating is we're taking the science and the understanding and saying, what can we do next with it to improve health? What can we, whether it's a widget or a policy or some sort of interesting outcome that ultimately makes someone or hopefully lots of someone's feel better in the long run? Sure, we're in a time of a changing job market. How does this program help students respond to that? Well, our students are actually quick and concerned about career possibilities. They are talking amongst themselves. They are looking for all kinds of information about how careers, how their education is going to allow them to advance their own careers. And I think there's a consensus that the old way of having a career for life in a single position, for example, is no longer the only option, in fact, is probably going to be the minority option in the future. Students are aware that in order to be able to take advantage of all the opportunities that are going to be out there, they are going to need not so much degrees, but rather skill sets and specific knowledge that will allow them to take advantage of those opportunities. Our program is really designed to do that, to allow our students to acquire those skills that they can then take pretty much in almost any direction in the biomedical space. We think our students will be highly regarded in startups, in biotech, in pharma, in CROs, contract research organizations, government, academia. I think the skills that we are going to be teaching them are things that will be transferable in a number of areas. So Joseph, people who are looking for more information, where can they turn? Well, you can look us up online at trp.utoronto.ca. You can send the program an email at trp.medscience at utoronto.ca. That's great. Thank you. | ↗ |
| 171 | MACRENE actives | Dr. Macrene Alexiades MD PhD — Harvard Degrees, Yale Faculty & World A... | 778 | 2 | 1 | 47.2 | neutral | 0:17 | Believe it or not, I have three Harvard degrees, an undergraduate, a medical degree, and a PhD in genetics, and then I went on into dermatology at NYU and happy to say that I am a dermatologist and a scientist. | ↗ |
| 172 | VJRegenMed | Developing iPSC-derived MSCs for therapeutic purposes | 188 | 4 | | 47.2 | | 1:45 | Thank you very much for that question because it's core to what we're doing at the bone therapeutics. It's really bringing in technology, IP and know-how and materials to complement what we already have in MSCs. As I said, we want to take MSCs of different origins and educate them, professionalize them for therapeutic benefits. So we're going to look at MSCs not just from bone marrow, but looking at IPSEs. I mean, the field of IPSE is expanding. Regulatory-wise people are more comfortable. There's IPSE-derived cells in the clinical trial. We aim at delivering MSCs from IPSEs and then educate gene-modify growth factor influence those MSCs into therapeutic cells. Bone therapeutics leading product alloc is already one asset like that. The following assets will go into inflammation and other conditions, really because we know that MSCs can deliver an effect, like for instance on graph versus those disease, but they can't that effect is not ideal. We can optimize it. And the technology we're getting from implant in terms of IPSE sourcing, in terms of epimonogenic MSCs, in terms of gene editing ourselves, will enable us to take the platform of IMSC. I as in use changed IMSC forward to obtain MSC based, Selon gene therapy product professional for therapeutic objective. | ↗ |
| 173 | CryoCord Stem Cell Bank | Induced Pluripotent Stem Cells (iPSCs) | 62 | 1 | | 47.2 | | 2:42 | In 2006, Shinyaya Manaka made a groundbreaking discovery that transformed the world of stem cell research. His work earned him the Nobel Prize in 2012 for discovering induced pluriponin stem cells or IPSCs. But what exactly are IPSCs? IPSCs are stem cells that can be derived from adult cells such as skin or blood cells. Through a reprogramming process involving the insertion of specific genes, these cells share many similarities to embryonic stem cells. This allows IPSCs to develop into any cell found within the human body. They are really the mother of all stem cells. Now, to understand IPSCs better, you need to know about potency, which refers to a cell's capacity to differentiate into many cell types. IPSCs, known for their strong pluripotency, have the potential to develop into any of the more than 200 body cell types, making them valuable for disease research and treatment. What really sets IPSCs apart is the way they work in reverse. This innovation enables cells with previously limited differentiation potential such as unipotent or multipotent cells to transform into any cell type. IPSCs, known for their strong pluripotency, can be turned into many cell types such as beating heart muscle cells. IPSCs and IPSC derived cells or extracellular particles are currently widely used around the world and clinical trials, proposing possibilities to develop treatments for some diseases. This makes them super useful for studying diseases, medical therapy, and finding potential treatments. Beyond their scientific significance, IPSCs also address ethical concerns associated with the extraction of embryonic stem cells. Furthermore, IPSCs can multiply indefinitely, ensuring a consistent and abundant supply of high-quality cells for research and therapies. Cored PSCs are IPSCs derived from cord blood stem cells. These stem cells are reprogrammed into IPSCs. In Southeast Asia, cryocord is the first company to offer IPSCs storage service. Leading the way in advancing cell-based research and medical possibilities. | ↗ |
| 174 | Mayo Clinic | Innovation to Impact: Regenerative Medicine for Consumers | 3541 | 7 | | 47.1 | | 2:31 | I think what constantly motivates me as well as my colleagues is just is the patience. And so we went into medicine to help people. We're really motivated to come up with new treatment options for people. What excites me about these orthobiologic options we have is that it opens up new options for patients. For patients with musculoskeletal pain who either are not candidates or are not interested in surgery, Mayo Clinic Sports Medicine has a few unique options. Some of those unique options are injections such as orthobiologics. The huge benefit is avoiding surgery. By doing that, you're avoiding complications from a surgery, whether that's anesthesia-related complications, but also avoiding larger incisions, which oftentimes requires a longer post-op recovery. And so because we're using a smaller incision, there's usually less recovery involved. Mayo Clinic is one of the leaders in providing orthobiologic injections to individuals. And it's not that we're inventing new substances to inject, but what we're doing is taking a look at the composition of these substances, taking a look at the outcomes of individuals after these types of injections. The safety of these injections is definitely a priority at Mayo Clinic. We are only doing procedures and injections that comply with the FDA regulations. And that's for the purpose of patient safety. We're evidence-based in what we're doing. There's a lot of hype about these different injections. There's a lot of hype about these different procedures, but we're guiding what we do and guiding what we're looking into based on the evidence, based on the science. That's really unique about Mayo Clinic. I love having that ability to say to someone, we have something else to offer. We can consider this. It's encouraging to patients, it's encouraging to me because I want to see them improve. That's what's most exciting about these injections for me. | ↗ |
| 175 | REPROCELL | Bioreactor Culture of iPSC's with ABLE Biott | REPROCELL | 1883 | 26 | 1 | 46.8 | neutral | 4:18 | The human body consists of about 60 trillion cells. And all tissues and organs are cell assemblies. It all begins with one fertilised egg, which divides repeatedly and changes into various types of specialised cells to form tissues and organs. These processes to determine the roles of cells are called differentiation, a cell which has differentiated once in the body will never return to its undifferentiated stage and its proliferative abilities also limited. This means that organs and tissues that are lost or damaged due to accidents or diseases cannot be regenerated in many cases. However, this conventional wisdom has been fully overtaken by IPS cell technology. Transducing just four genes into differentiated cells made it possible to return them to the undifferentiated stage. As IPS cells have the ability to differentiate into any type of cells throughout the body and also have a high proliferative ability, it is now possible to realise regenerative treatment through the fabrication of alternate tissues and organs. For that purpose, large-scale IPS cell culture technology is required. Heart disease treatment, for example, needs more than one billion cells. To culture so many cells, manually it demands a huge number of culture solutions and considerable time, as you can see here. To solve this issue, our research team tried using the 3D stirred suspension culture system, which uses a reactor. The impeler of the reactor agitates the culture medium three-dimensionally. Undifferentiated cells with a high proliferative ability will increase in number through division and then form cell aggregations. However, human IPS cells are vulnerable to physical stress. If the flow of the culture medium is disturbed, they collide with other cells or the reactor's impellers and do not proliferate well. To counter this problem, the research team revised the shape of the reactor's impellers. As a result, the culture medium began flowing literally at a constant rate and collisions with other cells or the impellers ceased. Using just one reactor, we could successfully culture as many human IPS cells as when using 50 culture dishes. Compared to the conventional manual method, this has realized a space-saving, highly efficient and low cost method of cell culture. Through the administration of certain proteins and compounds, we successfully achieved highly efficient differentiation into myocardial cells. To provide the large quantity of IPS cells that will be required for future regenerative medicine research, we are planning to produce larger reactors and increase their number. With the mass supply of IPS cells, regenerative medicine will move on to a new stage. R&D and the drug development field will be accelerated by using tissues made from IPS cells instead of those from laboratory animals. In addition, clinical applications using IPS cells for various human tissues are about to start. Our ultimate aim is the fabrication of organs. To operate regenerative medicine technologies in an integrated manner, we will complete the organ factory, thereby forging a new treatment path for countless numbers of patients. | ↗ |
| 176 | SCCTSIatUSC | Careers in Clinical and Translational Research - Dr. Allison Orechwa | 843 | 9 | | 46.8 | | 1:39 | Hey, I'm a neuroscientist and a dancer with an MBA, and I work in clinical and translational research. No matter your skill set if you are passionate about health and innovation, then there's a place for you in this field. Clinical and translational research is the type of science that leads to better medical treatments and disease prevention. In this field, scientists team up with doctors to invent a solution to a health problem, then with the help of big research teams, they test whether that invention actually helps patients, they test whether hospitals can use it reliably, and whether communities overall health improves. Who is on these big magical research teams, you ask? Experts come from all backgrounds. Scientists in ethics, engineering, finance, writing, technology all work on important steps in the process. Key roles include research coordinators who work with study volunteers and statisticians who analyze the data. Then there are community health workers who talk about the research with everyday citizens and also convey their opinions and needs back to the research teams. This writer spread the message about new discoveries and public health policy makers work to ensure equitable access. If this sounds exciting to you, follow this link to learn more about getting involved. | ↗ |
| 177 | Translational Medicine Foundation | Semmelweis University Translational Medicine PhD Program | 1443 | 10 | | 46.7 | | 12:50 | 1.7 Million Heaple under 75% under 75 die every year in Europe, but 1.2 million lives could be saved with more effective prevention and care. Meantime, 1.4 million articles are published every year, but most of the information they provide is not used in everyday patient care. So how can these scientific findings be put in practice as rapidly and effectively as possible? That is the key medical challenge of the 21st century. Translational medicine or TM speeds up the practical application of scientific results to find answers to questions asked at the patient's bedside and thus links clinical and basic research networks. A new TM model developed on the initiative of the academia-Europea focuses on providing healthcare, achieving new scientific results, summarizing these results in lay person's terms, and effectively communicating scientific knowledge to stakeholders who are patients, healthcare professionals, pharmaceutical companies, and decision-makers. The chief characteristic of TM is its multi-disciplinary and the cornerstone of TM is a registration system that covers all clinical fields. Translational medicine has four major parts and this is a cycle so you start from the patient's side and you come back and one part of the cycle is science and science is always almost nothing new just everything which is in front of us but nobody could seem before, nobody could notice about what is there. Therefore, like one of the healthcare delivery science methodologies, the methanolizes which actually summary and the new analysis of all the published data and summarizing this all knowledge can generate new knowledge, new observations in the field. When we attend patients and when we care for patients we can do science and we can answer scientific questions while we are making them feel better while we are giving them a cure while we are operating on them or doing an endosal before them. So basically, translational medicine enables clinicians to learn ways how to practice science and ultimately that is the aim of translational medicine as I see. The TM cycle model was introduced in Hungary in 2016 and the program has proved its effectiveness in the intervening years. Recognizing the significance of TM, Semauvice University in Budapest founded the Center for Translational Medicine in 2021. An institute of higher education with a strong 250-year history, Semauvice University is the leading medical training facility in Central Europe and the largest healthcare center in Hungary. The mission of Semauvice University is to get into the top 100 universities in world ranking and into the top five universities within Europe. For this we need to increase the scientific output but we are on a very good way because for example in the cardiovascular sciences we got into the top 55 universities in one of the ranking. We are currently building up an internal research development and innovation supporting system and the Translational Medicine Center is a part of the supporting system, a very important part of the system. This new approach to TM has further renewed PhD training. Our educational model of learning by doing took shape in 2016 under the leadership of Peter Hege, the current course director of this unique PhD program. Since then nearly 50 PhD students and residents have taken part in the training and over 300 quality publications have appeared. The results have made it possible to develop and supplement numerous patient care guidelines and to put scientific results in practice immediately. This education program is being carried on at Semauvice University on a much larger scale. Indeed almost 90 students were admitted in the first year in 2021. It's absolutely new method. It's absolutely new everything in this topic and the candidates can possibility to learn how can we write an article, how can we publish an article, how can we set up a writing this article. So that's why I think it's very useful. The program provides PhD students with the opportunity to choose from among eight research areas. Working in groups, students are able to acquire the necessary knowledge and skills as effectively as possible and thus conduct more productive and goal-oriented research. The PhD program covers all aspects of the TM cycle. It teaches students how to be critical consumers of medical studies, how to collect primary data through questions and observations, how to manage patient registries, and how to conduct biomedical research. Doing a PhD or participating in a PhD program was not a question for me. I have always been interested in science. The center of the program is based around translational medicine and mainly around clinical medicine and that's a really really important part of our everyday work. The whole system, I had this impression that this is a place where really professional work is going on and during the last six months I experienced it in person that this is really how it seemed in the beginning because we have a constant help from Professor Helle from our senior methodology supervisor from the statisticians and it's a very good feeling that we are not alone with our research and that everybody's interested that we make progress. So for me it's a very reassuring and a very positive experience. The Center for Translational Medicine assists PhD students with an interdisciplinary research support staff. Group leaders are experienced medical scientists with great expertise in their field of research. Expert discussants support students in writing their studies from planning to publishing. Supervisors help bridge theoretical research and clinical practice with the participation of an IT team and an ethics coordinator. Furthermore the program provides an opportunity for senior PhD students to play an active role in teaching. I started this program last September so that means now I'm a second PhD, second year PhD student and and currently I work as an SMS that means a scientific methodology supervisor and my task is actually to provide help mailing in the methodological issues to students. So we are kind of a bridge between the first year PhD students and the supervisors. With this special PhD program I'm working with two independent students related in pediatric oncology topics. So with this work we have to like a daily routine work at least two or three hours and refresh every previous day and extend it with further work. The program is very well detailed, very well organized in the way that we have the group meetings weekly and we have also the support of the whole team and from our supervisors is a way that they can be very effective with us all the time so I think it really helps to truly bring results very quickly that's what we can see today. Students in the TM PhD program are also prepared in how to establish contacts what communication strategies to use and how to present. Special training sessions are held to aid them in presenting their results as confidently as possible. The main language of the course is English the language of science worldwide. Every phase of the training proceeds in this language with quarterly progress reports in the first year of the course requiring students to hold presentations and answer any questions in English. We should be able to present progress from data to clinical evaluation what I mean we should present for us plot and to be able to take it into clinical context so what does the data mean and what is the implication for the research and for our daily practice. Our major aim that the first year they concentrate heavily on scientific activity and at the end of the year they would finish the two projects which required for PhD and in a year two they will mostly concentrate on health care but still have protected time one day each week for science. Those who enter the program will complete their PhD with a dissertation of high quality. They will understand and interpret the role of scientific research in the TM cycle with precision. They will also become skilled in setting up patient registries initiating clinical studies or conducting broad systematic reviews via meta-analyses. Further their lives may well be enriched with countless friends and shared experiences. I think actually the method we are using here in the Center for Translational Medicine is the most effective way to translate actually these data that we have in vast amounts now in the scientific world but now we are trying to find use for this and to implement the knowledge that they mean to us in the clinical practice right by the bedside and as soon as we can and as effective as we can. Those who wish to take an active part in the main goal of translational medicine renewing health care with results that can be measured in terms of human lives are encouraged to apply to the PhD program at the Semelvis University Center for Translational Medicine. Together let's bring science to patient care. | ↗ |
| 178 | ICU_Dr.Pradeep Rangappa | Immunomodulation in Sepsis | Dr. Pradeep Rangappa | 980 | 31 | 2 | 46.7 | positive | 23:39 | No transcript | ↗ |
| 179 | STEMCELL Technologies | Development and QC of SCTi003-A - A Highly Characterized Human iPSC L... | 926 | 9 | | 46.7 | | 7:11 | Hello and welcome to this informational presentation on the development and QC of the Healthy Control Human IPSC line SCTI003A. My name is Andrew Gaffney, Director of Stemsell Manufacturing and Commercialization at Stemsell Technologies and over the next few minutes I'll be walking through some key points about our highly characterized IPSC line. Now it was essential that our commercial IPSC quality assessments and release criteria were developed based on recommendations from a number of internationally recognised groups. That includes ISCBI's Banking Consensus Publication in 2009, Gates Paper on Clinical Grade IPSCs in 2018 and the guidelines rolled out by the ISCCR Standards Initiative in 2023 for the best practices and quality standards for human stem cell use in research. We took on board all recommendations from ISCR and implemented these guidelines fully into our IPSC development processes. And here they are, this is exactly how we develop and test our IPSC lines at Stemsell Technologies. All of the QC procedures that we use in production are listed in this table who are very open about how we do this and as you can see a number of cell banks are generated for each line including a master, working and commercial cell bank. These banks are approximately three passages apart from each other and QC tests are performed at varying stages of the development process. Now as a side to QC we also recognise that a lack of guidelines for naming PSC lines has led to some confusion in the field. So we decided to use the Standardized Nementlature established by HPSE Reg that unambiguously identifies a registered cell line. As you can see in the sensor of the screen our Healthy Control IPSC line has been named SCTI0038. If you scan the QR code on the left you'll see that this takes you to the official page on the HPSE Reg website for the 3A line and that contains all information relating to donor information, ethics, derivation, among other things. You can also download a copy of our extensive 25 page certificate of analysis from there as well. We've provided heightened evidence that the 3A line is pluripotent and has been donor-consented with the highest of ethical standards. Because of this HPSE Reg officially certified the 3A line showing that a minimal set of ethical and scientific standards have been met. This certificate is essential for certain funding agencies including any PSC research funded by the European Union. Now it's important to note that donor tissue is ethically sourced at SAMSEL and is collected using institutional review board or IRB protocols. In the case of 3A this was derived from PBMC's from a 48 year old female who was clinically undiagnosed donation. Dona characteristics are separated out by those that are self declared such as race and ethnicity and those that are calculated like height, weight and blood type. All of our QC can be broken down into a number of different parts, a selection of which can be seen on the screen now. This includes viability and recovery assays, detection of adventitious agents, identity testing, genomic stability and integrity, whole exome and genome sequencing, assessing the undifferentiated states by marker expression and assessing pluripotency by trial and age differentiation. Now in 2017 Florian Merkel and colleagues reported that whole exome sequencing of hundreds of PSC lines identified numerous mutations in P53. Separately to this, Shinny Yamannaka presented findings of a point mutation in the Tumor Suppressor gene B-Corp that also went on to be further described by group at the Sangre Institute. These findings drew attention to the acquisition of mutations in Tumor Suppressor genes in PSCs, so this is also a key focus for our analysis. We performed whole exome sequencing of the 3A line which allowed for the identification of genomic SNPs and the resulting profile of genetic variants was compared against ClinVAR. The statuses of P53 and B-Corp went on to be interrogated in depth. For P53, seven variants were detected and for B-Corp, there were five, however the good news is that they were all silent. Most importantly, no variants were identified that were previously reported by Merkel, Yamannaka and the Sangre Institute, and no pathogenic or likely pathogenic variants were identified by ClinVAR. I should note that despite focusing largely on QC in this presentation, a large amount of the work that went into commercialising the cell line was to demonstrate its compatibility with a number of differentiation protocols, some of which can be seen on the screen now. We've successfully differentiated this line into cell types of all three embryonic germ layers, as well as 16 other cell types, including neurons, cardiomyocytes, and microglia, and organoids, including intestinal, cerebral, and brain region-specific organoids, and that was all performed using our stem diff kits. Finally, we also tested the 3A's ability to scale up in PBS bioreactors. Cells were expanded in teaser A-O-F3D, an animal origin-free bioreactor medium. The linear log cumulative fold expansion plot showed consistent expansion with no lag phase during transition into 3D, and we saw an average daily fold expansion of 1.5. In general, we find that a total of 1 billion viable cells is reached after about five passages. And with that, I'd like to say thank you very much for listening. SCTI-003A is available for use in your laboratory now, and if you'd like to explore further data and information about the line, feel free to use your phone camera to scan the QR code on your screen now or visit the website directly at stemcell.com forward slash SCTI-003-A. You can also contact us with any questions or feedback at IPSCRequest at stemcell.com. Thank you very much. | ↗ |
| 180 | Queen's University Belfast | MRes Translational Medicine | 559 | 7 | | 46.5 | | 3:42 | We feel translation medicine is like a crucial bridge that enables us to take discovery sands right through from basic sands discovered at the bench, forward into the development of diagnostic tools and potential therapies for patients. I think we're beginning to realise that this whole area of personalized medicine now is a key and no matter what the disease is. For most cases most diseases it's there's no one cure if it's all I think or there's no one treatment for it's all. The key component of the master's programme is actually research so this entails a research project with a dissertation and that actually accounts for two-thirds of the the CASS points or the credits. As well as that then we have the research projects based on which stream you into. We have the Precision Counter Medicine, the diabetes and cardiovascular medicine and the infection inflammation and immunity. We now have drug discovery as a fourth strand which we're quite excited about in this sort of cover all aspects of drug development right through from identifying hits in the labs and to actually making drugs to take forth into clinical trials and patients. The projects are actually submitted by research active group leaders here. All of these are internationally renowned scientists. M.R.S. students are only working alongside PhD students and postdocs in the lab so they'll be working hand in hand with the team that's already here. A part of the project's actually for them to attend the seminars given by international speakers. So we have a weekly seminar from somebody from outside. It comes in a lot of these people are like more leaders in their particular field and the students then are invited to have a tutorial with the speaker and they sit down and have a talk. We have a module which is from concept to commercialisation. That particular module in conjunction with the Queen's Business School takes us a lot about the various aspects of biotech for example, spending companies, entrepreneurship leadership. We want to obviously teach research techniques to the students but on top of that we want to prepare them for all our aspects of medicine, all our aspects of biology. There's sort of applications that will make them competitive in terms of going for a job. We get a lot of students coming from obviously locally from Biomedic Science and the Human Biology Biochemistry courses here in Queens. We also get a lot of international students. We get a lot of clinical academics and we get medical students for example doing intercolletists here. That will give them extra points for their application and their foundation years one and two. And I think the M-rest gins will be exposed to a whole plethora of different applications. Some of the students will be getting hands-on experience in some of the sort of state of the art techniques that we have here. You know the legs of the large scale that aren't a seek and next generation sequence and as well as that we'll be able to align them to actual perhaps patient summals as well because we've dragged access to the Northern bad thing which is actually contained within our center. We have very close ties with industry here as well which makes us very attractive so we actually have within our center CCRCB. We have a couple of biotech firms embedded in the center and they have actually employed some of the graduates from here. I think that the bottom line is can we take this forward to benefit real people? Can we come and see drive improvements in global health across a whole range of areas, cancer, cardiovascular, medicine and infection and immunity? | ↗ |
| 181 | VJDementia | iPSC-derived 3D organoid models to explore Alzheimer’s disease | 894 | 8 | | 46.3 | | 2:32 | I think that it's a great enhancement for science, the possibility to use IPS-based models. So there are a lot of advantages mainly due to the fact that we can use patient-driving IPS, but we can also make genetic through CRISPR-Cas9 and using isogenic IPS that express only the mutation that we need in order to dissect the impact of that mutation on a particular phenotype instead of having a background influence on that. It could be hard, so I mean, it's strange to think that something like neurodegenerative disease could be studied using neurodevelopmental models because starting from IPS, even though we can arrive through three months or four months or five months development, they were still developmental model and not degenerative models. But it has been demonstrated that this type of mutations mainly also on towel, for instance, we have also did on that. They already impact on the neuronal size, neuronal formation, neuronal morphology and also in the synaptic activity. So we can see from the beginning in the organized model in the cell lines derived from IPS, things that maybe will have a strong impact in the huddle-tod and not in the development. And another thing is that moving from 2D to 3D system, this is a very nice example of how much increasing the degree of freedom is improving our ability to find things because thanks to the extra cellular matrix in 3D, is it possible to find the bitarmyloid aggregates that you cannot see in 2D culture? So I think that organoids can offer a very nice model to study both neurodevelopmental but also neurodegenerative diseases. | ↗ |
| 182 | Dr. Raut's Centre for Reproductive Immunology | Lymphocyte Immunization Therapy (LIT) v/s Passive Immunomodulation - W... | 449 | 6 | | 46.3 | | 3:53 | Welcome to our video on the differences between lymphocyte immunization therapy and other passive immunomodulatory treatments in case of reproductive failures. Today, we will explore these two approaches and understand how they differ in addressing issues related to reproductive health and reproductive failures. Before we dive into the specifics, let's briefly understand what reproductive failures are. Reproductive failures refer to the inability to achieve or maintain a successful pregnancy. Various factors can contribute to these failures including immune system abnormalities. Now let us see what are passive immunomodulatory treatments. Passive immunomodulatory treatments are designed to modify the immune response without actively engaging in the patient's immune system. So these treatments often involve the administration of antibodies or other immunomodulatory agents which can affect the immune system. Some examples of passive immunomodulatory medications or substances include intravenous immunoglobulin or IVIG and intra-liquid therapy. These treatments aim to modulate the immune system's response and create a favorable environment for successful implantation and successful pregnancy. Now let us see how lymphocyte immunization therapy or LIT differs. LIT immunization therapy or LIT takes a different approach. LIT involves actively engaging the patient's immune system to produce tolerance towards father's lymphocytes. How does LIT work in LIT? Mother is immunized with father's lymphocytes and this process aims to stimulate mother's immune system to recognize and tolerate paternal antigens. The underlying theory behind LIT is that certain immune reactions against paternal antigens can lead to reproductive failures. By exposing the mother's immune system to father's lymphocytes, LIT aims to promote immune tolerance, reducing the chances of pregnancy complications. This is achieved by producing protective antibodies called as blocking antibodies or asymmetric antibodies and also by producing certain type of protective cells called T-regulatory cells or T-rex. So LIT creates immunological conditions similar to those seen when pregnancy is protected naturally and hence it is more effective than passive immunomodulation and effect is also long lasting. However, it is important to note that LIT and other immunomodulatory medications are complementary to each other. It is important to note that the efficacy of LIT is still a topic of debate in the medical community. While some studies suggest positive outcomes other show limited benefits. However, more and more recent studies have now documented the beneficial effect of lymphocyte immunization therapy. If you are experiencing reproductive failures and you are considering lymphocyte immunization therapy or any other immunomodulatory treatment, it is crucial to consult with a qualified medical professional. They can assess your specific situation and provide personalized guidance on the most appropriate treatment options. We hope this information has been helpful in understanding these two different approaches. Remember, knowledge and guidance from medical professionals are absolutely essential when it comes to making decisions about your reproductive health. Thank you. | ↗ |
| 183 | Allergist Mommy | Food Allergy Fix - Immunomodulation is a Dance | 223 | 4 | | 46.3 | | 1:47 | The process of immunomodulation can be thought of as a dance with two partners. The doctor playing the role of the lead partner and the immune system playing the role of the following partner. Initially, it may seem to be kind of a mess with a lot of stumbling and stepping on toes. The lead may not be in tune with the partner's natural movements and the partner and the follower may not yet be ready to allow the lead to lead. The same goes for immunomodulation. At the onset of food allergen desensitization therapy, it may appear that the immune system is actually resisting being coaxed into a particular direction by the medical team. However, as time goes on, we'll find that the two start to move as a unit. Instead of stepping on each other's toes and having herky jerky movements all over the place, it'll start to flow. And eventually, the immune system will start to just respond very nicely to manipulation by the medical team and will be able to coax it into the right direction. The end result looks effortless, but we know better. | ↗ |
| 184 | Peter Attia MD | Exploring the utility of stem cell therapy | Peter Attia & Adam Cohen | 58671 | 957 | 214 | 46.1 | negative | 16:55 | Where do stem cells play a role here? Now we're going to talk about stem cells through all of these joints, but we might as well start here. When I hear that the tendons of those muscles and those muscles themselves are going to weaken, when I hear that my cartilage is going to weaken, when I hear that the, you know, the osseus structure of the bone is going to weaken, all of these things make me wish. I could just have newer and younger cells there. Right. So what do we know about the utility of stem cell therapy here? What's the state of the art today? Right. So, you know, this is a, this is a great conversation. And there's a lot of layers to this conversation because there's, you know, the dark side and the bright side of this. The, you know, we talk about ortho-biologics or biologics in general. Basically, biologics, it's a, it's a class of therapies that are using your own natural resources to promote healing. So you're using a biologic product to encourage healing of diseased or injured tissue. So the most commonly used ones are blood, specifically platelets, bone marrow, bone marrow aspirate concentratus called, and also fat. So if we sort of go through those three, just to start there, the, for PRP, what are we doing? So we take your, platelet rich plasma. Platelet rich plasma. We take your blood, we draw it, and we take it down the hall, and we spin it in a centrifuge. And the centrifuge machine will separate out the different elements of the blood based on the density of those elements. So after you're done spinning it, you have a layer called the plasma layer, which is rich in plasma and platelets. And it separates out the red blood cells and a lot of the white blood cells. Now you could spin it twice, you could do two spin technique, you can spin it so that you're keeping some of the white blood cells. So we've categorized it into leukocyte rich PRP and leukocyte poor PRP. And this is a very simplified way that we think about it right now. And there's certainly, if we fast forward 10 years from now, this will be a ridiculous conversation. Because we just are sort of in our infancy of understanding what we're doing here. So the principle is we take those platelets, which are involved in healing. We know this because if you cut yourself, the first thing that happens is the platelets come to the surface to form a blood clot and to form a scar and then you heal. So platelets are associated with an incredible amount of growth factors and healing factors, including the 800 to 1,000 proteins within the plasma. And you inject that into tendon, a joint with arthritis, muscle, and see what happens. So the problem is that as a physician, you are allowed to do that procedure, right? So there's no, there's no rule that can't say that anybody comes in and they say, I have this injury. Can I have PR, can I have stem cells? And you say, oh, sure, let me give you PRP and I spin it and I inject it. So, but what is the actual science say about what's actually working? And what we've learned is that it works for some things pretty decently and other things not well at all. And we can only go by our randomized controlled trials and systematic reviews of randomized controlled trials to find out what seems to work. So what are the, what are those best case scenarios? So tennis elbow seems to work with PRP. There's good data to suggest, like tier one data, maybe tier two data that suggests that it works for tennis elbow. It works pretty decently for gluteous medius tears. And for tendons, that's about it. Some will argue maybe in the hamstring tendon it works, but I'm not convinced. And just to be sure, are you talking specifically about PRP or are you talking about the broader umbrella of stem cells? broader umbrella of stem cells don't seem to work. And I think it's important to bring up a very important part, which is these aren't stem cells. And I think that's one of the major problems is that there is no stem cell therapy anywhere. Unless when you go to Mexico and get stem cell therapy, what are you actually getting? I don't know, but they're not stem cells. I mean, the only stem cell, I mean, I can only speak what's happening in the United States, but the only stem cell therapies approved in the United States are for leukemia, blood disorders, blood diseases. There is no stem cell. In fact, the FDA has a big warning page with a video that explains there are no stem cells. Stem cells implies that I'm going to inject cells into you and those cells are pluripotent. They have the ability to become something else and those cells are now going to become your cartilage. They're now going to become your tendon. That doesn't happen. In fact, right now, what seems to be happening? What's the identity of the stem cell? In other words, what is the signature that allows that doctor to know or at least believe they have a stem cell? Because these are not a tolligus, typically at these clinics, right? Aren't they... You know, someone else is... I only say that because everybody I know is basically going abroad, although I know some people that have done this here. They tear the rotator cuff and they go and get stem cells injected and six months later, the rotator cuff is fine without surgery. Sort of that type of thing. And it goes. Yeah. That first of all, it's illegal to actually give stem cells. So a few years ago, people were able to get products that were manufactured by companies who were selling umbilical cord blood or some derivative of umbilical cord, some umbilical product as stem cells. Wartons jelly, it's some of it's called exosomes. All these things are not allowed. The FDA will not let you inject this into anybody. And what's the reason for that? So the FDA has a division that will... That regulates the use of human cells, tissues and products. Even if a tolligus, even if you're even if they're your own. You can use your own as long as it's not manipulated or what we considered minimally manipulated. So spinning is not a manipulation? Spinning, that's right. So you can take your bone marrow out of the pelvis and we get it from the pelvis and you can concentrate that. But you can't give any enzymes to it, you can't digest it, you can't make any changes to that product. You can only give it as is. Now with fat, because fat has actually shown some promise with osteoarthritis of the ankle, very good studies on ankle osteoarthritis and fat injection, same with knee. You can do that because you're not... You're minimally manipulating the fat. You are taking it and making it into smaller fat particles, but you are not essentially altering the fat itself. And those... I mean, you're basically breaking down adipose tissue into individual fat cells? It's micronized, it's called micronized. It's micronized fat. And the idea is that micronized fat regrows as cartilage? No, it still doesn't. What does it grow as? So that's what we don't know. So right now, our best understanding of biologics in reality is that it reduces symptoms. It is symptom modifying treatment. And it's a good symptom modifying treatment when it works because we don't have a lot for, let's say, arthritis tendon problems. Our toolbox of things to use when someone comes in with knee arthritis or hip arthritis are pretty pathetic. It's... You're going to go to PT because that's mentioned on the help. I'll give you a brace maybe that might help. Maybe take some Cox-2 inhibitor anti-inflammatories and some cream, right? We don't have... The repertoire of what I prescribe is pretty pathetic. The non-surgical treatment for these things is pretty... So here's an opportunity with the ortho-biologic field to reduce symptoms in a safer way than, let's say, cortisone. Because cortisone is quite effective and safe as long as you're not injecting over and over again. So there's a space for this that is very reasonable. And the randomized control trials show that it works for knee arthritis probably better than anything. But the bigger... I think if we're looking forward as to what this... Yeah, what we're going to do... I know we have bigger... Why don't we have RCTs that can answer these questions definitively? Because there are a few things that I discuss with people in medicine that create more... sort of polarization around treatment than the use of these biologic therapies where the people who have had these procedures will swear up and down by them when they work, which is you don't understand. I couldn't move my arm and in six months I was fine. Of course we don't... We always fail to have the counterfactual here, which is possible your arm was just going to get better on its own. Correct. It's possible that the initial MRI showed something, but the follow-up MRI didn't show something. We're just healed on its own because it was going on its own. So the only way you can ever escape that is with randomized control trials. Are they being done? Yes. And so to that point, if we inject saline into somebody's joint, a number of those patients are going to get better. So that's sort of the standard we use. How does PRP work in comparison to saline? And there are a lot of studies. There are dozens of studies randomized controlled trials looking at PRP. And many of them have excellent results. The problem. And that's, for example, tennis elbow... For knee arthritis. For knee arthritis. That's probably of all the data, that's the tier one best data. But we know so little about this because it doesn't seem to work well in hip arthritis. And why do you think that would be? Is it just possible that the studies haven't been done correctly? Maybe. And I think this brings up a very important point. When you do a randomized control trial, let's say for a medicine of hypotensive medication, you know what dose you're giving. And you're comparing it to some other treatment where you know the dose. Plate lit, platelet rich plasma. I'm taking your platelets of unknown concentration. I'm unknown quality. Of unknown quality. I'm spinning it in a machine, either once or twice, and a different machines concentrate those platelets differently. And so then I end up with a product, with a certain amount of platelets. And then I inject it back into you. I don't even know your disease process specifically. So when you put people into a large number, into these studies, you get a lot of crappy data. So what the future holds is, and there's a push in our industry, and there's a particular association called the Biologic Association, which is like an association of associations internationally, where they've formed something called the BARB, which is a Biologic Association registry, and bio, it's a bio registry. It's a registry and a bio registry. That is, they have lots of centers, and they want to know everything about what you're injecting. They want to know what's the concentration of the blood of the patient. And what percentage of docs who are regularly giving this therapy are participating in the registry to the point where we can generate information? Very, compared to the total amount, very few, but it's enough people that we can get really good data to find out what's the aplicot, what's the dose, what's the critical dose of platelets that we need to affect change? What is, and other things, we can look at that, we can do a proteomic analysis of the actual fluid itself, and you match that with outcomes data from the registry. So you have a bio repository and a registry combined. Who did well and what did they get? And they save samples of that stuff too. But at best, this can only inform what an RCT should do. Those data by themselves don't tell us anything, right? Correct, but this gives information about to actually lead to the trial, right? So you say, okay, it looks like this works. Let's try this particular dose. So right now, PRP looks more effective at reducing symptoms than cortisone in the knee for arthritis. Is there any reason to believe it can delay the requirement for a total knee replacement? So maybe we know that if we look over the course of a year, because this is what those trials looked at, cortisone works very well in a short time frame. It's pretty impressive. The first couple of weeks you get one and it helps. There are some people who the pain comes right back. So it doesn't have staying power. When you compare steroids to PRP, the PRP, if you look out of over a year, they're doing better. Haleuronic acid, which is another thing we inject. Also is doing better than cortisone if you look out. If you combine, isn't Haleuronic acid considered biologic? It's not. Because it's an FDA approved product. It's yes, and I don't even know that it's a drug. I think it's even classified differently like a device, but I'm not 100% clear on that. So there's a number of studies, or I don't know about a number of study, I know of a very well done study that looked at Haleuronic acid and PRP together, and that seemed to be more effective, not astronomically more effective, but more effective than the treatments that we have. It's more effective, the combination of those two. But is it disease modifying? And that's the big maybe, because that's your question. And there are studies that show it may be pushing off knee replacements for those patients. But I think this is where we still don't really know yet, but there's so much deceitful behavior out there. With regards to stem cell therapy, that the organization's involved and the N, the FDA and the Federal Trade Commission, NCMS are all trying to crack down on the problem of people advertising, come onto my clinic, I have stem cells, I will inject it, it's 100% guaranteed to help you, I'm gonna give you new cartilage. And one of my colleagues at NYU did a study where they looked at a thousand websites, and 94% of those websites who were promoting stem cell therapy were making inaccurate statements. And it just, in gender's distrust between doctor and patient, when you're going for a treatment and you think they're telling you something that, I had a friend, I really, this is about two weeks ago, my close friend from high school sent me a brochure because he wanted to get an injection from his doctor of something like an umbilical cord or Wharton's Jelly injection, which is not allowed. And I look at the brochure, I said, send it to me. And I made the bigger and I circled it, and I'm the brochure, because it's from the company, the company sells it to the doctor, the doctor gives it the patient. On the brochure, it said, this is not intended to treat any condition. I was like, when I just circled it, I send it back to him. Never mind. | ↗ |
| 185 | Science Animated | CLOVES Syndrome Community: What are human induced pluripotent stem cel... | 1312 | 8 | | 46.1 | | 4:49 | Clove syndrome is a genetic disease caused by mutation of the PIC3 CA gene, which results in tissue overgrowth and blood vessel irregularity. The vision of clove syndrome community is to improve the quality of life of those affected by clove syndrome. To carry out careful assessment and consulting outside experts, CSC identified a gap in the clove's research strategy. They have therefore formed external research partnerships with the aim of developing new models to help improve understanding of clove's and its many manifestations, as well as to create tools to combat the disease. One of these tools is a cell model called induced pluripotent stem cells. These are the building blocks of all human tissues, the muscles, organs and even the brain are made up of billions of cells, each of which has its own specific function. Early in a person's development, as far back as the embryo stage, many cells don't yet have a specific function. These are called embryonic stem cells and have the characteristic of being pluripotent, meaning they can become any cell in the body. Cells have studied these cells to better understand how tissues in the body develop and how they respond to different stimuli. Pluripotent stem cells can only be collected from embryos. Cells collected at later stages of development are already assigned to a specific tissue, such as skin or bones. This limits their use in developmental research as they're already destined to become and remain one type of cell. Human researchers extract cells from embryos, they usually do this on animals, as doing this on human embryos brings an ethical dilemma. However, results from animal studies don't always translate to humans. Therefore, using human cells is the best research approach. How can researchers study human development and disease without using stem cells from human embryos? Researchers overcame this obstacle in 2006 when they discovered that mature human cells could transform into stem cells under certain conditions through a process called reprogramming. These reprogrammed cells are called induced pluripotent stem cells or IPSCs or human induced pluripotent stem cells, HIPSCs, when the original tissue is from humans. This breakthrough has allowed researchers to study the human specific development and disease. To generate HIPSCs, researchers take a biopsy from a patient and set apart a single type of cell, such as a skin cell. They then reprogram these isolated material cells, turning them into HIPSCs using just full proteins. Under the right conditions, HIPSCs can become any type of cell in the body. Most of these researchers need to make a few modifications to the DNA of HIPSCs, such as adding or removing a pick-3CA mutation. Once they've made these modifications, they can store the HIPSCs and use them as required. A key advantage is that both the variant and normal HIPSCs have the same origins, which means the healthy and clove cells can be directly compared. These can now use HIPSCs to examine the particular tissues affected in clove syndrome, such as the blood vessels or skin. By culturing healthy and clove's affected cells together, researchers can also investigate how healthy cells and variant cells communicate. They can also apply pharmacological treatments to the transformed cells, for example the breast cancer medication, a palliative or apomycin, which have shown promising combating clove. Additionally, researchers can screen new compounds on HIPSC-derived cells for use as clove's treatments, helping to expand the range of available treatments for clove's. Clove syndrome community is not only advancing HIPSC research, but we're also invested in creating other research methods for scientists to use. Check back here for future updates on the clove's tools we're developing at CSC. | ↗ |
| 186 | California Institute for Regenerative Medicine | Beating heart cells made from stem cells | 51022 | 971 | 1 | 45.9 | positive | 0:07 | No transcript | ↗ |
| 187 | The City College of New York | Spotlight on the Master’s in Translational Medicine Program | 2905 | | | 45.8 | | 4:31 | Hi, I'm Jeffrey Granitsch and I'm the director of the Masters in Translational Medicine Program at the City College of New York. There is an overwhelming need to increase the efficiency with which we translate basic biomedical research into practical solutions that can be used to treat patients in a healthcare setting. The MTM program here at City College was conceptualized and developed to fulfill that need. The program is an intensive one-year master's curriculum that is based around a biodesign project in which students form teams and actually build medical technology and test it in a clinical setting by the end of the program. The curriculum covers topics from intellectual property through to regulatory affairs, reimbursement strategy, business case, and translational challenges in bringing a new medical solution to market. Be in vision that students with some type of STEM background will be interested in this program, whether that be an engineering background, a medical background, students who are either practicing physicians or have aspirations of going to medical school and those interested in doing research in a clinical setting. So I have two primary goals for the future of the program. First is to prepare students to go out and really have an impact in some capacity based on their interest in the job we do as a community to bring new medical technologies to market and to treat patients. The second goal, which is number one A, is for City College to be at the forefront of the development of this style of program. If I look at biomedical engineering as a discipline over the past 20 years, I see tremendous growth and I really think that this style of master's program is in a similar position and I'm very excited that here at City College we're at the front of that. We're one of the first handful of programs of this style in the country and I'm really excited to help develop that and develop this style of program over the coming years. So graduates of the MTM program to date have gone on to pursue medical training and work in a clinical research setting. Over time as the program grows and our class sizes grow, I envision that roughly half of our students will want to work in medical or medical technology product development setting, whether that be the large company or whether that be at a start-up that they created themselves. The other half, I envision, will pursue either medical training or return to their medical practice or research in a clinical setting. My name is Cedic Roman and I'm a student in the Masters in the Translational Medicine program in the City College of New York. So for my undergraduate career, I also went to the City College of New York and I majored in psychology as well as my under-biology. I was on the pre-med track and I was ready to start medical school but I also wanted to see what other options I had to help out patients in the real world besides medicine so that's what kind of drove me to apply to the Masters in Translational Medicine program and that's where I met Dr. Gratige and Dr. Stukes, leadership of the MTM program which convinced me that they were invested in their students and that I was a great fit for the program. On applying to the Translational Medicine program, I knew that it was heavily emphasizing biomedical engineering and while I didn't have your traditional engineering background, I did have a STEM background that allowed me to smoothly transition into the courses that I took and I soon learned that we would not only learn about biomedical engineering but we would also be focusing in on commercialization as well as entrepreneurship because both are important to medical devices and building. This led me to create my own team and enter the Zon competition where we were semi-finalists when we built an app for chronic pain patients and it's really exciting to see how far we've come and this is greatly due to my time at the MTM for words that best describe my CCNL experience are diversity, mentorship as well as opportunity. Diversity in that, I've been free to take as many classes and different subject areas as well as meet different people from all around the world that kind of shaped my whole experience at CCNL. Mentorship because I'm undergraduate now in graduate career, I met so many great professors that helped me along the way and opportunity because there's always an opportunity out there to kind of showcase my skills that I've learned here at the college. | ↗ |
| 188 | AdtU Digital Learning Platform | Immunomodulation & Natural Medicine | 377 | 5 | | 45.8 | | 14:44 | you you you you you you you you you you you you you you you you you you you you you you you you you you you you you you | ↗ |
| 189 | CTSI-CN | Dr. Srinivasalu: Immunomodulation and Cytokine Profiling in MIS C | 84 | 3 | 2 | 45.8 | positive | 18:15 | No transcript | ↗ |
| 190 | Lica Doctor | #dermatology #youth #medicalaesthetics #longevity #stemcells | 172 | 1 | | 45.7 | | 0:47 | Feeling is easy, regeneration is medicine. For years, aesthetic treatments focused on adding volume, but volume alone does not create youth. Youth is skin quality, density, elasticity and glow. You can smooth wrinkles with filler, but if the skin is thin, tired and dehydrated, your age is still visible. That's why modern dermatology is evolving. Today we focus on regeneration, volume, nucleotides, exosomes, PRP, PRF, peptides. These treatments stimulate your own collagen. Improve microcirculation, restore skin, thickness and activate natural repair. Want to know more about youth and health? Message, longevity and comments. | ↗ |
| 191 | National Science Foundation News | How Regenerative Medicine Is Rebuilding the Human Body | Podcast | 3376 | 87 | 7 | 45.5 | positive | 21:36 | No transcript | ↗ |
| 192 | University of Helsinki | Studying Translational Medicine – Straightforward to become a research... | 2480 | | | 45.4 | | 2:46 | I'm Juan, I'm from Argentina originally, but I studied in the Faculty of Science of this university. I'm in the final year of Transmed and I am working in a laboratory for mitochondrial medicine. So it was pretty straightforward to become a researcher here because it usually Transmed students are pretty valued in the labs and it's quite nice that usually the offers go around and then we can do some kind of internship and then we can start with a thesis project or some trial period. My plan for now would be to stay here for PhD since some of my projects will go forward to the doctoral studies and I have some other side projects that will also join that and then in the future probably staying academia or go to companies but for now, pre-PhD for sure. The study program in Transmed was pretty well designed to fit all the cutting-edge knowledge of the field. It really combines pretty nicely the medical knowledge with applied specific scientific technologies and I think it was very useful, especially being in the same building as most of the research labs that was quite handy because then I could work at the same time as attending the lectures and learn things that I could directly apply in the lab so I think it was very nicely coordinated. The atmosphere in Transmed is very international usually like most people are international students and there is also some fins so it's really interesting to be in such an international environment and have to usually a lot of the courses are involve a lot of group work and discussion and that's really nice kind of to learn how to interact with other people from other cultures and practice English of course and then just work together for that and it generates quite a quite a nice group. Housing is a pretty great city to study and I personally really enjoy it. It's very easy to settle down, everything works very nicely and is very well organized and then studying here I mean all the studies are in English and usually most people are pretty good at speaking English so it goes very smoothly and I think the student life is very interesting and I really like it. Finnish universities are different in my opinion to other places because they usually put much less pressure or stress on you and it's usually depends up to you how the speed you want to do your studies in and how much you want to coordinate it with sidewalk so it really I feel that it really allowed me to work at the same time and work at my own pace and at the end most of us ended up doing it in the right time but there's much less stress behind it and not so much kind of pressure. | ↗ |
| 193 | Salk Institute | Cell reprogramming leaves a "footprint" behind | 1975 | 3 | | 45.4 | | 1:33 | The purpose of our study was to really look for the first time in high resolution at the epigenomes of both embryonic stem cells and induced pluripotent stem cells. What we learned from this study was that embryonic stem cells and induced pluripotent cells overall look fairly similar, but what we found is there are differences and these differences can be identified in different types of induced pluripotent stem cells and it differentiates their epigenome from embryonic stem cells. So this allows us to identify a signature of the reprogramming that hasn't been fully completed in induced pluripotent stem cells. This IPS signature will allow us to try to understand the mechanisms now that differentiate ES and IPS cells. Now that we have identified those locations we can begin to carry out experiments to ask what's missing in the reprogramming events. Why aren't these IPS regions reprogrammed properly? The epigenetic signature is there in many different types of IPS cells so we know that it's a parameter that happens every time you carry out the assay and so it provides a way of distinguishing ES and IPS that we didn't have before. | ↗ |
| 194 | CRGchannel | ENG - Cellular reprogramming: a real tool of regenerative medicine? - ... | 1024 | 6 | | 45.4 | | 15:01 | so it's very important to in the general public to make science because this is uh increase awareness about what we do in the lab first of all and increase sensibility to fund research and then of course people understand much more what is science about so that we are trying of course to to find solution but not all I do believe that to bring science in the general public uh is the mission of a scientist so we do not have only to stay in the lab but also to make this uh available to to everybody this in the long run we push politician to put more funding and and not only politician but also company and uh any foundation that can fund science if is something that goes from one cell to an adult so one cell can divide and give rise to two cell this one cell is very toy poent divide and give rise to two cells then eight cells and to um the Mora and the blastos from the blastos that is 3.5 days and AR to an embryo which is formed from three different tissue which has called or mesoderm endoderm and ectoderm this little mass of cell which is called Inner Cell mass and this group of cells basically give rise to embryonic stem cells we in the lab can isolate embrionic stem cell from this group of cells that derive from an embryo 3.5 days post Fertilization in a mouse or 5 days in a human so these cells are very toy poent so they can generate each tissue of the body body they can be propagating indefinitely and they can differentiate in each cell of our body differentiation is when you take a stem cells and this stem cell can give rise to arthrite lymphocyte muscle cell or neurons any cells but this process that seems very easy is very tightly regulated normally what you have is that from a stem cell you have another stem cell that is called a progenitor cell or adult stem cell so for example an adult stem cell of the nervous tissue can give rise to neuron olenite or asites for example the lineage development of the of the mattic system start from an another stem cell that is called hematopoetic stem cell and this as you can see in these slides can give rise to a plora of different progenitor cells this cells here can differentiate in the cells that is called CNP and CNP can differentiate in M or GMP and so on but the interesting things that I want to point you out is that at each branch in the end can give rise to this cell line or this cell line so mcroof or ainop but it cannot give rise for example to rroy there are other stem cells that are multipot that is different to be toy poent because they can differentiate in some cells and not in others you can have adult St cell in the brain in the heart in the bone marrow that can give rise to specific cells of that particular tissue this is what is differentiation is a stepbystep process that an a cells that is a stem cell become more and more committed until it becomes a differentiated cell these cells they beat as as the hair a stem cell that we have IND used to differentiate in a cardom myosite in the differentiation is something unidirectionally from a stem cell you can go to a muscle cell to a fiberblast to a cardom myosite you can go to a fiberblast that is a skin cells and and then you can go back to a stem cell and then you can differentiate again this cell in another lineage so this is was really a change of the paradigma I mean up to last century it was thought that differentiation was unidirectionally but this is wrong so reprogramming is when you go back from a somatic cells to a stem cell is an increase in poy or the differentiation and therefore I mean we know very little about we don't know if it or in nure and the moment as I said is a a a technical laboratory to produce uh let's say stem cell from somatic cell one of the very early experiments demonstrate that the fate of a somatic cell can be reversed back to a stem cell phenotype and this was through nuclear transfer you can transfer the nucleus in a a nucleated orite what happens is that this you generate a clone so the nucleus of the different a cells is completely back to a stem cell phenotype but can also generate several clone animals so in this way we have changed the fate of the nucleus of a somatic cells and make possible that this new entity the Crone can generate a new organism there are others method one is that you can basically make an extract of stem cell or make an extract to all sides and then this you can basically put on somatic cell and this you can induce partially ear programming not stable but nevertheless you can induce some reprogramming also by this method another method that is through Cell fusion you can take a different differentiated cells and you can really fuse with a stem cell so then you have an hybrid here there was an experiment in in a lab from Dr Schuler they took uh the cytoplasm without the nucleus and this was fused with a somatic cell and in this case they did not get any reprogramming in contrast when they Fus the nucleus of the stem cell with the different cells they got reprogramming the factors that induce reprogram are in the nucleus of the stem cells and not in the cytoplasm of the stem cell you take this Gene and you put this gene into the nucleus of the somatic cell what you will have is that with a very few genes you can convert this cell into a stem cell like or what is called IPS this was the experiment of yamanaka they took a differentiated cell they expressed these four factors here through a virus and then they could generate an IPS cells that give rise to could be propagated like embryonic stem cells or or they could generate mice there is another method which is the lineage reprogramming you can make a direct conversion from one cell to another without passing through the pl poent state so this method have been identified specific factors which can do this conversion to conclude this part to wrap up what I said it was stood for a long time that these are all you know separated box from an emonic stem cell you can have ectoderm meod and anoderm what I told you really at the beginning and it was told that there was not possibly you know way of passing from one box to another but more recently with two different approach one is through self Fusion or through the expression of specific factors now we know that you can push differentiation back and you can really pass from one differen cell into into another now what we can do with this there are several applications or dream project and one of the dream project is that you can create IPS and you might might cure a sick organ so this is a dream project because it's really I mean we are very far to reach to this point we are studying the mechanism controlling reprogramming and so there are group of genes that in the balance between differentiation and and stemness they keep the maintain the stem phenotype there are group of genes that maintain the differentiated phenotype what we try to do we try to silence uh the genes that induce differentiation to keep the stemness phenotype these are the four factors that the Japanese uh researcher yamanaka used in his first experiment these are not essential so they can be substitute by other factor or by other modulating other pathway so they are all not essential at the moment the use of this IPS is in the clinic is not even in in the clinical trial phase you can find also these 10 top things to know about the stem cell treatment there are different type of stem cells there is not a universal stem cell therapy that will cure any types of disease or any type of conditions there are very few accepted uh stem cell therapy currently just because people say that stem cell help this does not means that they do why takes so long to uh to develop new therapy because science is going very slow when when you do a stem cell therapy you you have to instruct cells to become what you want they have to become as much as we manipulate in vitro in culture as much as we induce differentiation and therefore cells lose their potency and they likely is more complicated to handle and to let the cells to do what you wish uh they should do there are a lot of uh treatment for sale that are not um are very very risky also because clinical trial take a lot of steps to authorization to go really into the clinic nevertheless we do believe that stem cell science is an important field and and we hope that in the end we will really have something important for regenerative medicine we are mostly concentrated in self Fusion mediated reprogramming why because it's a very very efficient way to induce reprogramming we do believe that it might be a physiological mechanism Fusion is a process that occur normally during development it occurs during fertilization it occurs during the formation of a specific tissue in the placenta or during the formation of muscle of bone some people that believe that Fusion can be a mechanism to repair or regenerate a tissue and we are studing exactly this so what is regeneration first of all it's something that in the lower uh ukar like in fish or in amphibians it happens naturally and one example of this a particular uh frog is the salamander after the amputation these cells here they undergo the differentiation and then they redifferentiate again and in the end they form again the the Lim of course we don't have this ability to regenerate our hands if we have an amputation unfortunately but this means that during the evolution this is something that have been lost from lower ukar to higher ukar but can in a way be stimulated so we are trying exactly this to stimulate this process what we are doing in the lab and this our working hypothesis is that you if you have a damage somewhere in your body you can have some circulating Bomar cells that confuse with cells that have been damaged to make it easy is a signal that can activate the cells and tell the cells looks you are to become very potent and you have to activate this group of genes okay we do believe that there is a reprogramming of the hybrids that are generating after fusion and then finally a regeneration of the tissue we have done this in vitro and now we are using a lot this approach to to try to to regenerate or to cure or to enance uh regeneration in in several disease model what we believe is this schematized here research that things that can trans differentiate or become something different in other tissue or after Fusion can become something different but we do believe we do believe that a cell from the bom marrow fuse with a somatic cell and form these hybrids which then can be reprogrammed and regenerate uh tissue to conclude srael is a a painter of the Renaissance in Italy we do believe that reprogramming is like the zus that blows on the on the cells and these cells they can be regenerated as the Venus here represented and and we do believe that this painting represent a bit the process of reprogramming | ↗ |
| 195 | MetaVeil | Why Do We Age? #shorts | 286 | 2 | | 45.4 | | 1:35 | Every birthday candle we blow out reminds us. Time is catching up. But why do humans age at all? At the core is cellular damage. Every day, our DNA, proteins, and cell structures are hit by stress, UV rays, toxins, even normal metabolism. Our bodies repair most of it, but not perfectly. Over decades, tiny errors build up and cells lose efficiency. Another key factor is telomeres, the protective caps at the ends of our chromosomes. Each time a cell divides, telomeres shorten when they get too short, the cell can't divide anymore. This process, called replicative senescence, is one of biology's built-in clocks. We also age because of oxidative stress, unstable molecules called free radicals damage ourselves, add-in declining stem cell activity, and weaker immune defenses, and suddenly, recovery from illness or injury slows down dramatically. But aging isn't all breakdown. Evolution may have favored aging because it clears the way for new generations. Instead of one immortal being hogging resources forever, turnover keeps species adaptable and resilient. Of course, scientists are now searching for ways to slow aging, studying telomeres, gene editing, caloric restriction, and senolytic drugs that target zombie cells. Some believe humans may one day extend life far beyond today's limits. Still, for now, aging is the price of living. The gradual accumulation of times fingerprints on every cell. So would you choose immortality if science made it possible, or accept aging as part of life's design? Comment time marks below. | ↗ |
| 196 | VJDementia | Potential of iPSC models in Alzheimer's disease research | 278 | 4 | | 45.4 | | 0:52 | I'm really excited to work on a human-based model for Alzheimer's research, because although animal models have been extremely useful throughout the years to elucidate lots of mechanisms, we are also at a stage where clinical trials are kept failing and lots of people are thinking there might just be big enough differences between human genetics and mass genetics that we should be trying to work with human systems. And it's also a really good opportunity to try and screen lots of molecule first before we even need to do, for example, the animal models or the clinical trials. | ↗ |
| 197 | StemCellChannel | What are induced pluripotent stem cells? - Dr Andrew Laslett explains | 4755 | 23 | 2 | 45.3 | neutral | 5:08 | In juicepluoripotent stem cells, stem cells that we've made by putting in genes or factors that we know from embryonic stem cell research are able to what we call reprogram a cell an adult type cell back to its original state where it can become any cell in the body. So the great thing about induced puberty potent stem cells is that they're as able as embryonic stem cells to form every cell type in the body, but we can really easily choose which cell types we make them from. So whether or not it's from somebody that's healthy, we can make an IPS cell control, or we could potentially make IPS cells from someone with a specific disease to allow us to set up models of that disease in a dish to study in the lab. With IPS cells at the moment with the way they're made, we do not know whether they are safe for treatment of humans. The way they are made currently in the main is using viruses that can cause cancer. We don't know their long term stability and we really don't know a lot about them because they're so new as they were first created in a mouse in 2006 and in a human IPS cell line in November 2007. People are claiming is that IPS cells get around all of the ethical concerns with using excess embryos for the creation of human embryonic stem cell lines. There are a large number of ethical or ethical questions involved with the use of IPS cell lines that still need to be addressed in terms of the way they are. The way they are used in terms of the way they are generated is people need to give informed consent if for example they're giving a skin cell or even from a single hair cell now induced polypoten stem cells can be made. So they're not ethical free. They're not in an ethical free zone. We're still researching embryonic stem cells for a number of reasons and one is that we don't really know yet whether under all tests and conditions, IPS cells are exactly the same as human embryonic stem cells. That's actually the focus of one portion of my laboratory that's really carefully looking at that question. Also in any IPS cell research we need something to compare to that we know is truly a polypoten stem cell. So a polypoten cell is a cell that can make any cell in the body. So we need to be able to compare and contrast with human embryonic stem cells and I think it's also a fair point to make that without research into embryonic stem cells we never would have had IPS cells. At the moment we're comparing in a head-to-head fashion through a number of different tests testing whether IPS cells can make certain cell types within the body as well as human embryonic stem cells, checking whether they express all of the same genes and proteins and also really carefully looking at how stable they are and whether or not they form. Tumors when we put them into animal models. I think the potential for IPS cells is really quite huge. I think the jury is still out on whether these cells are going to ever be used to treat somebody directly but the information that we can get from them by using them as a tool to study them, study diseases in a DNA test. These diseases in a dish is limitless. They can also be used in ways by pharmaceutical companies as a screening technology to assess the effects of drugs, to assess whether drugs are toxic, to see whether common compounds we use are toxic on specific human cells that are being made without actually testing animals for example. | ↗ |
| 198 | VJHemOnc – Video Journal of Hematology & HemOnc | Effective immunomodulation with pomalidomide during induction TST for ... | 97 | 2 | | 45.2 | | 1:26 | I presented findings from a Phase I Dose Escalation Study of Act DVP-16 induction time sequential therapy followed by pommelidamide in newly diagnosed AML patients. And pommelidamide is an immunomodulatory drug, has protean immune stimulating effects, but what we are most interested in is to see if we can induce a T cell activation to enhance anti-luchemia immunity after chemotherapy. We dose escalated pommelidamide and we found that the safest dose was 4 milligrams for 21 days after induction chemotherapy. And so we found that pommelidamide was safe and tolerable at that dose, but more importantly, we found real significant clinical activity. We had a 74% overall complete remission rate with Act DVP-16 followed by pommelidamide, which again compares well against historical controls. And we were most encouraged by the unfavorable risk patient population, which does very poorly with chemotherapy. And we found 82% CR rate, complete remission rate in that patient population with this regimen. And we hope to move this on into further stages to really assess whether this drug can enhance activity in AML. | ↗ |
| 199 | Nuffield Department of Clinical Neurosciences | Generating human sensory neurons from induced pluripotent stem cells | 1495 | 15 | 1 | 45.1 | neutral | 5:20 | I'm just going to introduce our project in which we've generated human centrenure on from induced pro-apotent stem cells in order to generate a malinating co-culture system. And the reason we wanted to do that is it's really essential for healthy peripheral nerve function a very close and intimate relationship between axles and shwan cells. So axles are malinated by shwan cells and there's complex bidirectional signaling between these two different cell types. Now that signaling can go wrong in disease states such as inherited neuropathy, inflammatory neuropathies and we obviously want to understand that better, preferably using a humanized system in which we have the native proteins in their normal environment. And so to do that we've taken advantage of really this emerging technology which is induced pro-apotent stem cells. The principle there is we will take a skin barbeque from a patient, generate fiber blasts and then we can reprogram those fiber blasts with a number of oncogenic factors. We can then generate pro-apotent stem cells that can give rise to any cell type in the body but in this case we've differentiated them into sensory neurons. And then the aim of this project is to combine these sensory neurons with rodent shwan cells and really to understand if we can generate long term malinating cultures using this system and most importantly to see if we can use it as a model system to study disease. In order to establish the malinating co-cultures we first differentiate the IPS cells to sensory neurons, mature them for several weeks and then seed in the primary shwan cells. The subsequent alignment and onset of malination recapitulate exactly those same events that occur in vivo. So here you're seeing a live malinating co-culture. You can see the individual human cell bodies and the phased bright elongated structures are the malinated axons. We've performed cross-sectional electron microscopy imaging through these maline segments and you can clearly see the individual maline wraps and the surrounding basal lamina. Between each maline internode we see successful formation of the node of rombiae with correct compartmentalization of key nodal proteins including fortish-gated sodium channels at the node and contactin associated protein in the adjacent paranode. The shwan cell and axon are in very close contact and are constantly signalling to each other. One crucial pathway vital in the initiation and maintenance of malination is the nureglin a B receptor pathway. We've overexpressed nureglin 1 type 3 specifically in the sensory neurons using AAVs and we see a dose dependent increase in the levels of maline production. So this confirms that this vital pathway is active in our malinating co-cultures. So we've shown that we can successfully model the interactions between a human sensory neuron and a shwan cell in vitro. So the next step is to investigate a pathological scenario that impacts on the functioning of these two cell types. The development of a culture system involving the malination of human sensory neurons provided us with an viable opportunity to investigate the pathology of immune-mediated demanding nurepathies. In this study we primarily focus on the chronic condition chronic etaxic nurepathy with optalmplegia, m-protein, cold occluutins and anti-diysylosylantoblase, also known as canemate. The major reason for this focus is that this nurepathy has prominent and often disabling sensory dysfunction as Tony Morris began to experience symptoms of this disorder in the early 1980s, other struts. In the early 80s I started to feel my feet were very uncomfortable and I was generally walking very cumtsyly. A few years later it the numbness and the lack of control moved at my legs. This meant I didn't really have any balance so I couldn't stand or walk and whilst initially things were very uncomfortable and there was a lot of pain and discomfort. Once the peripheral nurepathy had spread throughout my entire body I lost all sensation of pain. The whole of my body had lost its sensation. By applying anti-diysylosylantoblase to our malignant co-culture system we're able to demonstrate both the topographical targets of these antibodies in culture and also their pathological effects. Antibodies were found to target the exposed nodal and unmalinated axolema as shown here. With the addition of a source of complement acute and extensive axonal degeneration ensued. However canemate has demilinating as well as axonal features. We speculated that if demilination was also mediated by anti-diysylosylantoblase then this bit may be via a more chronic complement independent mechanism. The impressive longevity of our cultures allowed us to continuously apply diysylosylantoblase over two four week periods both in the onset of malination and also in established six to nine month old cultures. These experiments revealed that this exposure both prevented malination and also induced demilination without affecting axonal integrity. This work is therefore established that anti-diysylosylantoblase have pleiotropic pathological effects. Co-cultures now provide an ideal system in which to further establish the mechanism of these pathological effects and also to test new therapeutic strategies. | ↗ |
| 200 | Everything ALS | Using induced pluripotent stem cells as a platform for ALS Dr. Nichola... | 1050 | 22 | 3 | 45.1 | positive | 57:49 | No transcript | ↗ |
| 201 | Thermo Fisher Scientific | Dr. Uma Lakshimipathy presents Generation of Transgene-Free Induced Pl... | 3357 | 17 | 2 | 45.0 | neutral | 4:53 | So to start with the most common method for using, for generating IPSE is transduction of the four factors shown here is the Yamanaaka factors. And after a black box even which takes anywhere between three to four weeks you end up with IPSE colonies. So the biggest bottleneck right now one is the efficiency of IPSE formation depending on what kinds of cells you start with the efficiency is really low. And the second thing the second bottleneck is how do you detect these emerging IPSE colonies depending on the expertise of the users and the field of pre-repertance stem cells. People can either pick it really easily or there's always like a issue on what clones you place here bet on. So when it comes to efficient methods there are several methods starting from viral, non-integrating and more small molecule methods such as mRNA, microRNA and small molecules. But one of the methods that we've really worked on is a non-integrating viral method based on send-i-virus. The reason why this method is superior to the other current methods is its efficiency. It is a non-based on send-i-virus which is RNA virus. So again coming back to the different methods that are out there. If you were to this is a graph that I took from a published paper. If you look at the efficiency versus the safety obviously methods such as small molecule, microRNA, RNA and protein they don't leave a footprint of the extremely safe to use in a clinical setting. However the efficiency of generating IPSE right now is pretty low at this point of time. The highest efficiency so far has been obtained with viral methods such as lenty and retro. More recently the cytotune which I'll show you some data actually excels the efficiency that you can actually get with the traditional viral systems and at the same time it's relatively much safer because it's RNA virus and it's non-integrating. Therefore it will not leave a footprint in the genome of the cells or the IPSEs that are created. So this is again a brief introduction. This was a system that was developed by a company in Japan called DNAVAC. The original paper was published. There has been several papers since then starting from generation of IPSEs not only with fiber blast but also blood cells. So I won't go into more details there. What I would like to show you is that using the cytotune system that we actually sell as a product the process of generating IPSE is extremely streamlined. The four factors comes in four tubes which can be transduced overnight onto maps. Most of our protocols right now are for fiber blasts but we are developing methods for other cell types mainly blood lineages. After it's a one time contact you don't have to do repeated transduction. So in that way it's really workflow friendly. After transduction you have to give it around three to four weeks. At the beginning of three weeks is when you start colony formation and at the end of four weeks you have sufficient colonies to pick up and choose. There are actually more colonies than you really want because there are way too many colonies there. What we've done here this method actually shows you that it's integration free. Using PCR we're able to show that there's no absolutely no viral genome left in the clones that were established. This is 10 independent clones that were generated. You can also use an antibody although I would say that the antibody is not very great because you can see the haze in a negative cell type and you actually can tell whether it's negative only when you have a true positive control because the positive staining is so much more robust. These cells are pluripotent both in their marker expression and differentiate into different lineages when randomly differentiated via embryo body formation. These clones were all generated on feeder dependent systems in case are based period but since then we've also been able to generate IPSE clones both and the feeder free conditions using a stem pro sfm media as well as xenofre conditions which is basically a case are xenofre media in the presence of growth factor cocktails on human feeders. | ↗ |
| 202 | RegenOrthoSport | What is Regenerative Medicine? | Dr. Venkatesh Explains | Ft. Ranveer | 380 | 4 | | 44.7 | | 0:47 | What is regenerative medicine? As we age or an injury. So you start wearing the jaw and you start wearing the cartilage, right? So you're losing, losing and your body is trying to make it. Sometimes it's hard to make it because some of these materials like your cartilage, ligament, tendon, do not have enough blood supply. So what happens, they continue to degenerate. So if we can regenerate that particular, say like the cartilage or a tendon or a ligament, that is called regeneration. The regeneration could be anywhere in the body. So if you have a heart problem, lung problem, kidney problem, anything that can regenerate, it tissue that is naturally degenerating is regenerative medicine. The human body is built to degenerate over time. That is what the process of aging is. Exactly. | ↗ |
| 203 | canalcnio | Tissue damage is key for cell reprogramming | 2884 | 20 | 1 | 44.6 | neutral | 1:39 | Cellular reprogramming allows specialized cells, such as those forming most adult tissues, to revert to stem cells. Stem cells are much more versatile and therefore have the ability to generate cells with multiple functions. Reprogramming requires introducing a particular combination of four embryonic genes into the adult cells. This process has been widely studied in isolated cells in the lab, however, little is known about how it occurs in the body. Researchers at the Spanish National Cancer Research Center in Madrid have observed that, when tissues are damaged or aged, they are much more susceptible to cellular reprogramming. Specifically, damaged cells activate alarm signals that favor the reprogramming of surrounding cells. Among the multiple signals sent by damaged cells, researchers have discovered that a previously known protein called interleukin-6 is essential for cellular reprogramming. This way, reprogrammed cells in the damaged tissue can generate the different specialized cells that are needed to restore the tissue. These advances have been published in the journal Science and could open new doors for the treatment of diseases such as Alzheimer's or diabetes and degenerative processes such as aging. | ↗ |
| 204 | European Association for the Study of Diabetes | EASD 2017 Immunomodulation - Chantal Mathieu, Matthias von Herrath and... | 429 | 4 | | 44.5 | | 12:19 | So now we'll talk about immunomodulation in type 1 diabetes. I'm here with Chantai Matieu from University of Løven. Matieu is from Herat, a professor and expert on type 1 diabetes and auto-cost green from University of Opsala. So where is the field currently and why haven't we cured type 1 diabetes yet? Well that's a question. I, as a clinician, very often get for my patients with type 1 diabetes and it's not because of lack of try. There's a lot of research on going worldwide, very high-level research and we are making progress. We are getting better insights into what is this disease that is type 1 diabetes and what we've learned is that it's really a very complex disease with not only what we taught a couple of years ago, the immune system just attacking the beta cell as a sitting duck and the beta cell dying. We've now also learned that the beta cell itself plays a very important role in its own destruction, sending out signals to the immune system and dying in a certain way. So it is a complex disease. Is it one disease? The diagnosis is made on just the clinical symptoms and it wouldn't surprise us as we gain more and more knowledge that we will be able to stratify these into multiple different diseases that end up with the same beta cell destruction and then the same clinical symptoms will develop. Certainly we need some form of stratification also for the trials. Because one thing that's slowing us down is that we have metabolic endpoints for the clinical trials and they often take some time and because also they heterogeneity in disease progression pathology, I'm not sure yet, but heterogeneity in disease progression that drives up the amount of patients you have to enroll for each arm and then the trials become long, complex and very costly and that's of course not accelerating things. But Chantal, we mentioned it, we're making progress. Absolutely, absolutely. But about the heterogeneity, again for the clinicians it's so obvious that a child who gets type 1 diabetes at two years of age is very different from the person getting it at 40 years of age. And as Mathia said, biomarkers, biomarkers that would allow us to better phenotype, characterize patients in order to get, if we get interesting tools to intervene, to give the right tools to the right patient and also to design better trials. And so there are many efforts on going, on finding better biomarkers and yeah, understanding this disease better. In a way it's an exciting time because now we have these big consortia like I am, I am an odia and so forth, like trial net where everybody begins to work together. And I think for finding proper biomarkers and dealing with large cohorts of people, that's absolutely needed, that's not a single lab or person's effort. And in a way it's an exciting time and an exciting time of progress. Yeah, and what is important is if we want to beat this beast, if we want to prevent or cure this disease, we will all have to work together. Not only academics, but also industry. And as Mathia said, in initiatives like in odia supported by IMI, you have the funders, you have the academics, you have industry and patients. Everybody working together, trying to get a better idea of how this disease is going and how can we really do something. But I think one of the biggest challenges we already said heterogeneity biomarkers, but another big challenge to me is the fact that we have no access to the organ where everything is happening. And as for instance, Ola has demonstrated, this is really very important because a lot is happening in the pancreas. And I would say also that the field is benefiting now of the technical development in parallel to the diabetes research. So imaging biomarkers, everything like that is also very interesting period in time now. Development is really, really fast in those areas. And my hope for the very near future is that these technologies will give us tools to stratify people and to bring into clinical trial, but also to help us in designing good endpoints of our trials. And of course in respect to the pathology, it would be really nice in a way if one of these days we understand what causes this disease. And as Chantal and Ola already referred to, it's complicated. We just now with access to the human organs begin to understand that's an interplay between beta cells and their immune system most likely, but there has to be also other factors, maybe environmental factors. We don't know them. We have a struck empty finding a virus that causes the disease that was a popular hypothesis over many years. And they have been these hygiene hypothesis, but we also have struck empty to identify a single culprit, but we need to look more because as there's no in feeling, I think you have this too that we might overlook something. You have brought forth interesting hypothesis about the pathogenesis. I think the field needs this to be a bit shaken up to make us think again. And maybe if we have the cure, if we have the cost then finding a cure for the disease will become easier, right? I think also that the type one like this is an orphan disease in the way that it's one of the most severe chronic disease a young person can be affected by. But in terms of funding, attention in the general public in our society, it's much, much inferior when compared to cancer or other diseases that also affect young people. So I think also we need to get an increased awareness of how promising the research are and that we actually are going hopefully to be able to treat our patients much, much better in the very near future and perhaps also cure the disease in some people affected. Interesting trials are running. I mean we are doing trials, but as Matthias said there's always this challenge of getting homogeneous group of patients to really be able to make solid conclusions and refute certain therapies. I think we've made some mistakes in the past like with the anti-CDT where we took very heterogeneous populations took very strange endpoints. So trials that are running now are typically trying to combine certain therapies. Therapists that might protect the bed ourselves together with immune modulation for instance and we try to get better, more solid endpoints that make more sense in preventing or arresting a disease like type one diabetes. It's absurd that you would have as an endpoint hemoglobin A1C in these days where you have analogue pumps and what have you. You know this is trying to arrest an autoimmune destruction of the beta cell. So we need to have markers of beta cell function or a beta cell mass that are really the endpoints and so a lot of effort is put into also convince regulators for instance to accept these endpoints in a disease like type one diabetes for instance CPAP type and that's not obvious it's very different from type two diabetes. And also one big problem in doing clinical trials is that by tradition the regulatory bodies in our countries often only accept one investigational drug to be tested and what Chantal is talking about is that we take home a sit from the entire field now is that we have to combine different treatment options. And where do you time the trials like at what stage of the disease or the patient? That's that's a very crucial question and relates a little bit to the issue what do patients really need and how much are they willing in a sense to pay or take in terms of side effects for them. That's one way why we need these combinations maybe to have more synergies with two different therapies but spread the side effects so the therapy becomes more palatable for the patients and we can also if we're talking about prevention then of course the benefit for the patient could be greater because you could stave off the disease for several years and there's little argument that that of course is a very strong benefit especially if you're talking recent on such trials there's now pumps there's better means to control glycemia there's sensors so the incentive for the patient to do something drastic becomes lower and the bar for the therapy in terms of no having no side effects and achieving lots becomes ever higher if climbing sort of in front of us and we would also like to salute all the patient participating in different tries. There is this altruistic attitude in the community so we can ask patients to participate in the trial that just would generate knowledge they would not benefit from being part of the trial but they are willing to participate just to help us to help other people affected even if they because individual cannot. Exactly and again also you know these patients are so supportive of all our initiatives and they help us to better understand this heterogeneity to develop better biomarkers another challenge is that very often we are dealing with children and also the first degree relatives of these children are children and so we they are so motivated to give their blood and other samples over and over again so indeed it is very important but then again it comes to Matias' comment about the bar we are treating children so side effects safety it is really a very big discussion when you think on the one hand we're trying to arrest all gym union destruction of the beta cell or improve the beta cell function but on the other hand we are treating young people for a long period of time and you know finding the right balance between efficacy and and safety and acceptance of side effects is what makes this also difficult. Yep and that translates to the timelines because often you have to test something in adults first if it can be done and I think that's fair so that takes longer before you can move it down the line in age to three and so the overall tries timelines to finding a new drug candidate and then having a face one safety and a face two maybe ideally combination that's like five years maybe if you're really lucky for the new candidate two years for the safety and some biomarkers maybe another trial for face two with more biomarkers so you're already a decade out and you're in the best case done with a face two trial whether you have to then take a step back and say does this qualify for face three it's it's not so fast for the right reasons I mean because of children being affected and because of safety but that was your initial question and of course the question from all the patients. Well thank you very much for participating in this discussion. Thank you. | ↗ |
| 205 | Cyagen | What are “induced pluripotent stem cells”? | 9594 | 4 | 1 | 44.4 | negative | 1:05 | Induced pro-reportant stem cells are a type of stem cell that are generated from non-pro-reportant cells such as skin or blood cells by introducing a combination of specific genes or molecules. In production of these genes, molecules reproduce the non-pro-reportant cells into an embryonic stem cell like state with the ability to differentiate into many different cell types. In the body, IPDCs have similar characteristics to embryonic stem cells, but do not require the use of embryos which has been a source of radical controversy. IPDCs are usually various areas of research, including disease modeling, drug development, and regenerative medicine. | ↗ |
| 206 | Case Western Reserve University | Anthony Wynshaw-Boris: Chromosome Therapy - Rescue of Ring Chromosomes... | 676 | 4 | | 44.3 | | 25:05 | first of all I'd like to thank Alan for organizing this wonderful Symposium uh and for our guests for coming all this way to give wonderful talks thanks so I'm going to talk today about a um novel system uh for abnormal chromosome correction that we uncovered uh in human cells and that is ring chromosome correction during induced furry potent stem cell reprogramming and as you can imagine this wasn't something that we set out to investigate although I have't studied uh genome instability in the past but we stumbled upon it when we were studying this disorder this human Disorder so now we're going to get away from yeast a little bit I think Stan's probably going to talk a little about human as well next we're studying this disorder we're studying for many years listen which is uh called which is refers to the smooth brain as you can imagine although the brains are very similar in organization brains miss the the normal gy and susai of primate development and so the children that have this have severe mental retardation seizures and early death there are many forms of lenuo but one of the most severe is Miller deaker syndrome and that results in a completely ayic brain here shown in this MRI and some recognizable cranofacial dysmorphisms at a medical geneticist of which G one could easily recognize all children with Miller deaker Syndrome have about at least a one megabase deletion on the tip of chromosome 17p that includes more than 20 genes including a gene called Lis one uh and although I'm not going to talk much about Evolution since evolution is the title of the seminar as well I just want to point out that we knew nothing about what list one did until its function was uncovered in the bread mold Aspirus nigin and was found that it interacts with dining and important for dining regul and function so that's my little uh forent Evolution for my talk so uh what we wanted to do although we found a lot out about the phenotypes and the mechanism of action of Liss one using Mouse models we were interested in trying to make human cellular models of this disorder and so in this case we're taking advantage of the recently described and now ubiquitous method of induced furry poent stem cell Generation by cellular reprogramming and as you all know this was developed by shamanaka who won the Nobel Prize for this several years ago and the the concept is you take a skin cell or any other cell from a patient and by uh transfecting uh transiently cells with four to six transcription and other factors those skin fiber blast will be reprogrammed into Pur poent stem cells similar to es cells and these cells can then be studied differentiated in vitro to any sort of cell type that one wants to study let's say again the disease is listen then one want would want to make brain cells study those cells and see what can go wrong for cellular disease model in addition if the genetic defect is corrected it could also be used for cell therapy in the patient if there is a Cell Therapy modality for the disorder so Marina burin a postto in my lab when I was at UCSF decided that she wanted to make these models and so what Marina did was to take three different patient cell lines with Miller deer syndrome and being interested in the history of Miller deer syndrome we wanted to reprogram this patient's line this patient was uh uh was uh born in the 1980s and a kype analysis indicated that the child had ring chromosome 17 and this is the first indication that any could be wrong on 17 for Miller deaker syndrome and so uh a number of other investigators then looked to see in uh other patients with Miller deer syndrome whether there was something wrong on chromosome 17 and in fact all patients had a deletion of the pr arm of chromosome 17 so this patient LED then the to the identification of the genetic cause of Miller deer syndrome these heterozygous deletions of 17p so Marina reprogrammed fber blast with a ring chromosome patient and two typically deleted patients first of all let me tell you a little about Ring chromosomes they form when um the PIR that normally protect the ends of the chromosome are lost or activated allowing a chromosome to form uh a ring and this could then result in both genetic and structural problems structural problems because ring chromosomes are diff difficult to uh uh undergo Division and uh genetic problems if there's any loss at either end as there is in Miller deer syndrome resulting in hin sufficiency in those problems so the Inus is quite rare but it can occur in every chromosome and there are human beings that have ring chromosomes in all of the autosomes as well as the X chromosome that have been described so these are known now one of the things that happens is that uh there's unstable behavior of ring chromosomes during mitosis there's a failure to pair with homologous chromosomes frequent wiing loss leading to monosomy there can be the formation of dcentric rings secondary ring derivatives and the formation of anaphase Bridges leading to genomic instability and because of that there's an increased rate of anupy and high cellular death rate in cells and culture in the patients themselves in fact patients that have no deletion resulting in any other abnormal phenotype almost always have small size so growth rate is reduced in patients to have ring chromosomes and that's almost Universal so we were able to collaborate in San Francisco with the the yamanaka lab and Marina was able to reprogram the patient fiber Blast from each of the three lines one with the ring and two typically deleted lines into uh IPS cells and those were proven to be I IPS cells because the cells were all able to make uh the endogenous factors that indicate that their IPs cells listed here also by inv vitro and inv Vivo methods were able to show that all the cells could uh contribute to all three germ layers maderm endoderm and ectoderm so in fact these cells were Pur potent the ring chromosome line as well as the two typically deleted lines all reprogrammed at about the same frequency and so when Marina first uh examined the fiber blast of course the ring chromosome as well as the typically deleted lines all had a reduction in both Lis one mRNA the gene that's at the edge of the deletion as well as another Gene coding for 1433 Epsilon ywh Hae in 50% levels and the fiberblast also had 50% levels of DNA however after reprogramming although the typically deleted lines had 50% reduction in list one genomic DNA the ring chromosome lines now had a normal level of Lis one genomic DNA they had the normal of list one mRNA and they also had uh Rescue of the to to normal levels of production of list one and 1433 Epsilon so in the fiber blast here's the level of wild type list one and 1433 Epsilon the typically the leaded lines and the ring chromosome line had 50% reduction in those proteins however after uh IPS formation that the typically deleted lines had 50% reduction those proteins but the ring chromosome line now had again correction to normal levels of these proteins and so the reason that that occurred this is published so I'm just going to summarize some of the data really quickly is that the ring chromosome that was in the fiber blast after reprogramming in several different clones the ring chromosome was lost and replaced by a completely normal chromosome 17 so that there seem to be two identical copies there and this uh occurred sometime around pass D this would just show the frequency of the Ring chromosome kot type in in doing kyp analysis in the fibr blast at two different passages and you can see that almost all the cells have the ring chromosome phenotype uh in after reprogramming the majority of the cells the vast majority of the cells now had a normal 46xy kyte so how did this correction occur or can we look at it by other molecular methods so what Marina did was use snip genotyping to look at copy number variants the ring chromosome fiber blast this would be all of chromosome 17 the P arm the croome the Q arm and this uh cluster of salmon colored dots shows that there's a a 50% uh deletion at the tip of chromosome 7 17p in the ring 17 fiberblast that was now corrected after uh the uh uh uh in the in the IPS cells that were made from there and IPS CS were made from the two typically deleted lines and they maintain their deletion again showed by the salmon colored region at the tip of 17p it's an important experiment because one possibility is that there are genes in this region when deleted would not allow reprogramming to occur but in fact since they were able to be reprogrammed that suggests that that's not the case in fact the deletion in this IP mds3 line is very similar in extent to the ring chromosome line so it doesn't seem that there's a genetic cause for this as well so Marina then looked tried to think about what potential mechanisms could have occurred and two occurred to us that were easy to test one is in the original cell with the ring chromosome there would be loss of the Ring remember I told you there's anupy in the ring chromosome lines and impatients and then by uh sematic non-disjunction there would be complete duplication of the uh uh normal chromosome another possibility is that there will be a double strand break occurring in the ring chromosome and after mitotic uh homologus or combination there would be then repair of the tip of the chromosome using the other normal chromosome as a template this is relatively easy to test especially with the snip array that we had before because in this case the entire chromosome would be homozygote because it would be duplicated and in this case only the tip of the chromosome would be now homozygote the rest of the chromosome would be heterozy we could use the snip genotypes that I showed you in the previous slide to test that out so here just shows the results from chromosome 177 uh and this would be from the fiberblast uh in the ring chromosome patient uh the the representation here is for the three potential genotypes so Snips are either A or B you could be heterozygous AB homozygous AA or homozygous BB and in the ring fibroblast line there was a mixture of all three genotypes in the IPS lines deriv from The Ring chromosome patient now they're completely homozygote either AA or BB while is while in the two different typically deleted lines that were made into IPS CS though those IPS C had a similar distribution of heterozygous and homozygous genotypes those patterns were also seen in every other chromosome in the IPS cells from The Ring chromosome line of the fiber blasts or from the typically deleted patients so it seems then like the mechanism of uh rescue is that in the fiber blast where there's a ring chromosome during reprogramming there's loss of the abnormal ring chromosome and duplication of the normal chromosome to restore a normal genotype uh the same mechanism works for other chromosomes so in this case we looked at ring 13 two different patient lines and again the fiber blast had ring 13 and multiple IPS clones derived from those fiber blasts from two different patients with two different Rings now had normal kype and normal uh distribution of of genes and by using the snip genotype that I showed you before also rescued by uniparental isodisomy so uh in summary then for this part of the talk there's ring chromosome correction in IPS cells that involves non-disjunction ring chromosome loss compensatory uniparental isodisomy and selection so what we think happens is that occasionally a cell loses the ring chromosome as it's going from fiber blast to the very proliferative State that's occurring during reprogramming and an early passage then if some of those cells lose the ring they may die but at later stages when the ring chromosome is lost and then reduplicating the other chromosome those cells will then be selected and after time either the ring chromosomes are lost or or the normal kot type is now over overgrown in the cells and it's again due to unial isod only so you can correct then the ring chromosome defect in fiberblast during reprogramming uh into induced Flur poent stem cells so again the Miller deer syndrome can be modeled uh ring chromosomes are frequently lost in IPS cells although I only only showed you information for ring 13 and ring 17 others have modeled tried to model ring 14 and ring uh uh 21 and they've also found similar uh uh phenotypes in that the the unipal isodisomy rescues those ring chromosomes the duplication of the wild type chromosome rescues monomi and compensates for the ring loss contemp cons compensatory uniparental isod diomi restores the normal kype and the normal copy number of deleted genes we think dynamic mosaicism in the IPS cells leads the preferential survival of the kot typically normal cells so that's all well and good for the 150,000 patients that have uh that have ring chromosomes but we're interested I'm a human geneticist and seeing this may have broader applicability it turns out that uh you may be aware that chromosomal abnormalities are actually quite frequent in about 50 60% of spontaneous miscarriages uh 4 to 11% of still births 5 to 7% of neonatal deaths half a% of live births and of course low frequency of ring chromosomes are found so it's actually quite a significant uh abnormality throughout the lifespan uh now if you think about correcting a varieties mutations in cells for for the purposes of uh of uh of uh regenerative medicine strategies then one way to do this if you have just point mutations is that you could take the somatic cells with the disease genome that is small deletions or point mutations reprogram those cells with the disease genome and IPS cells and then correct the disease genome uh with a variety of different genome editing tools such as crisper or tailin and now one will have mutation corrected IPS cells to give back to the patients um but in the case of of of chromosome aberration such as Miller deer syndrome how might you do that and so what we're thinking one could do is perhaps uh if a cell has large deletion or of course ring chromosomes that we shown then perhaps during reprogramming uh and selection and screening you can correct the IPS cells if you make the large deletions into ring chromosomes and then the ring chromosomes will either be lost during reprogramming or during the propagation of those cells and of course there's a lot of problems before we could ever consider using this and I'm not even attempting to say when we do this this is just a thought experiment at the moment because there are a lot of uh issues that might result in in problems such as genome instability imprinting or recessive mutations but I think some of those can be corrected at least by uh the genome editing and so one example I don't think tun's here but tahun Kim is a postto in my lab that's trying to do this he's trying to use genome editing to insert locks P cassettes into the ends of a chromosome that's deleted in this case the Miller deer syndrome chromosome region the cassettes uh will contain are containing a fluoresence marker as well as a cdna for another fluoresence marker TD tomato on the other chromosome there's a fluorescence marker and the the um promoter an atg for the TD tomato construct these are locks P sites that are also introduced in the same orientation on each end of the chromosome in two genes that appear to be uh uh not responsible for hin sufficiency so once those are introduced then tahan's introducing cre combines with the thought that if cre combin a will properly Rec combine and form a ring chromosome these cells will then Express TD tomato and these can be selected even if it's a rare event so tahon has gone through all this experiment he actually has has some TD tomato positive cells now that look like they're promising candidates for having a ring chromosome the problem is that they're pretty low in frequency so we're trying to find ways to purify those cells that we can do carot type make sure they do in fact carry the ring chromosome and then what's going to happen is if he does have cells that are TD tomato positive generated from the locks P insertions a cyan and cyan and Venus positive cell that now becomes a TD tomato tomato positive ring chromosome containing cell then further propagation will result in the loss of that ring chromosome loss of TD tomato and then perhaps duplication of the normal chromosome to rescue that phenotype now this may happen during Repro uh in propagation of the IPS cells we're hoping that that's what would occur if not we're going to have to do this correction to form the Rings in fiberblast or other sematic cells and in addition to trying to correct chromosome deletions we're also thinking to try to use this to actually model ring chromosome defects so there's some phenotypes that you might like to examine in in cellular model and one of those is ring chromosome 14 syndrome which even if there's no genes are deleted in ring chromosome 14 there seems to be a problem with gene expression on that ring and the children have very severe phenotypes particularly EP epilepsy so one would want to make a model of this but of course this correction mechanism foring chromosomes has so far not allowed this to occur so the idea would be if we can introduce lock P sites into chromosome 14 at the ends can we make an inducible model of ring 14 and then finally can we correct extra chromosome copies as alen was talking about such as tromis by perhaps again taking one of the extra copies say in triom 21 introducing lock P sites in the end forming a ring and perhaps uh growth selection will allow us to lose that ring uh and have restore a normal diploid complement to those cells in culture and the idea would be that these cells can be used either as models or perhap perhaps for regenerative medicine strategies in the future so uh again what I've tried to tell you about is there's a novel mechanism during reprogramming for the rescue of ring chromosomes we're going to try to exploit that for making disease models for rings as well as for potential cell therapy in the future and I'll just acknowledge the people did the work I pointed out Marina and tahan's major work again this is a collaboration with shinya lab particularly Yohi Hayashi and shinya lab other collaborators at UCS also helped in this project as well so thanks very much I'll be happy to answer any questions so my yes Phil destabilizes inist at right yeah and um oh keep and and were you suggesting that the reprogramming regime itself destabilizes the R over just mically propagating it's hard to say so did everybody hear the question is it is it the reprogramming itself that's causing the instability or simply the propagation of ips cells so we won't know until we try to do the experiment so the experiment that we're doing now of course is to do this ring chromosome formation in IPS cells so we think that it's the rapid proliferation of ips cells with a very very uh short cell cycle very very short G1 just they synthesize DNA and and actually then just divide so that rapid cell cycle is impeded if one has a ring chromosome and so the loss of that will then allow those cells to outcompete the other cells so we think that's one potential mechanism of how that could occur another possibility though is we make the ring chromosomes and the ring chromosomes are stable over many many generations in which case that would suggest it's due to reprogramming so if that's the case we now can make some other sematic tissues out of the IPS cells and then re- reprogram them and see if that's how that's happening but the key thing is to have a marker so cells that have the ring chromosome with TD tomato that we can fish out of a whole population and ones that are losing that so we can see how that's happening so the question is a good one hopefully we'll find out soon yes sense of how long 2us one so and can it divide or is it actually unable to divide until unless it shows some it so can how long will it take a 2 N minus one cell to divide a lot of it would depend on the chromosome presumably it will take a relatively short period of time where it can be uh 45 have a complement of 45 the exception would be the X chromosome because 45x those cells will actually can actually propagate quite quite well although not completely well um so so it may be that it's happening all at once that you lose the ring chromosome and duplicate the other chromosome it could be that the duplication is occurring first and losing the ring chromosome until we have a way to look at those cells by by sorting or other mechanisms that have a TD tomato positive cell we won't be able to address those so another possibility of course for making for doing these experiments is we can find more about the mechanism of how this is occurring and maybe even Pathways it might be responsible for the loss of the Ring chromosome yeah so if you with a ring chromosome and you partially dilize the spind with drugs do you lose the ring chromosome can you destabilize with drugs the the spindle in a way to uh change the kinetics of what's going on this so I think in general if IP in IPS cells if you slow down the cell cycle by a variety of means it's going to impede uh the plur potent state so that's what about fiber the original so they probably grow slower we didn't measure how fast that the fiber blasts are growing rather rather than other fiber blast lines because they're all primary cells and so there could be some differences there with passage um probably the more interesting question is why is this such a problem in IPS cells we can have human beings running around with ring chromosomes and I suspect it's just because one has uh so many divisions that are occurring in these cells in culture that you can't sustain ring chromosome for very very many passages uh and so they're lost in culture in a way that they're not lost in humans but that's another question that will need to be addressed hopefully we could do this in models as well is a phenotypic varability among individuals who are affected by ring chromosomes because if there is a loss of hyos would expect that you should get all sorts of things there's a lot of phenotypic variability in patients with wiing chromosomes for one it's uh it can be secondary to the loss of genetic material when the ring forms others it's because there is mosaicism among patients that have ring chromosomes so some normal cells some ring chromosome some cells in which they're breakage products a lot of it just depends upon the chromosome that's involved and as I described ring 14 it's a very interesting story because whether there's deletions or not the phen type seems to be the same there seems to be something because of the Ring 14 formation that may be silencing other genes on that ring chromosome and may be contributed to the phenotype so it depends upon the chromosome itself perhaps it depends upon what genes are brought together during the ring formation there could be position effects and it probably certainly depends upon the chromosome itself whether there's Hao insufficient chains on the ends or whether they're genes like ring 14 where there's suppression or some other mechanism that's causing that to happen yeah bill you any idea how fre DS are happening at the moment we don't and at the moment we don't we haven't tested that again I think we're going to need to purify uh in some way what's happening we can look at what happens after the ring forms by purifying those cells and then having those cells to examine later at some point I think that's what we're going to have to do okay thank you | ↗ |
| 207 | StemCellsGroup | What Is Immunomodulation? #shorts | 302 | 2 | | 44.2 | | 0:23 | Stem cells don't just repair tissues, they also modulate immune system. This is called immunomodulation, a smart way to calm inflammation and reset immune responses. The sacramental stem cells release bioactive molecules that guide immune system to reduce overreactions, like in out to immune diseases. It's not suppression, it's violence. That's the power of cellular intelligence. | ↗ |
| 208 | Keck Graduate Institute | Benefits of the MS in Translational Medicine: KGI's Eemon Tizpa | 380 | 3 | | 43.6 | | 1:11 | My program is I do a collaboration with City of Hope and it's the MS in translational medicine. So this program as translational medicine is defined is to try to bring pharmaceuticals from like a wet lab scenario to the bedside. So with the use of City of Hope's resources, we're able to have a lot of vast opportunities to work using like state-of-the-art techniques and methodologies such as like CRISPR-Cas9 with the use of like high throughput sequencing and working with very like well-renowned researchers in order to attack like very booming topics in like the biomedical field such as like diabetes, cancer and like other very serious disease such as like HIV and autoimmune diseases. So it gives me that ability to become more familiar with the biomedical field and at least understand how difficult it is to go through the publication process especially with these like very like upcoming novel therapies that are coming out like you kind of develop a appreciation as you read through these papers. So it kind of gives you a sense of appreciation and more of a sense of understanding through the process. | ↗ |
| 209 | ADictionary | Immunomodulation Meaning | 971 | 1 | | 43.3 | | 0:29 | Immunamodulation Any of several adjustments in the level of an immune response? IMUMUMUMODULTIN Immunamodulation | ↗ |
| 210 | University of California Television (UCTV) | The Immune System in Regenerative Medicine | 30915 | 732 | 18 | 43.2 | positive | 57:11 | No transcript | ↗ |
| 211 | Boston Children's Hospital | Induced Pluripotent Stem Cells (iPSC) Part 2: Research and Therapy | 1064 | | | 43.2 | | 1:42 | As a physician scientist here at Children's Hospital, I see lots of kids with a variety of both genetic and malignant conditions that affect the blood in the bone marrow. I see kids come in with sickle selenemia. It's a very, very painful illness that's caused by a single abnormal base, a single point mutation out of the three billion pieces of genetic code in their cells. And yet that single abnormal molecule results in tendency for their blood to become thick and sludge in their vessels and cause excruciating pain and adeterioration in organs over time, the heart, the lungs, the kidneys. That's a very devastating disease. And yet we can now study that in a petri dish. We can take sickle cells from a patient, put them into a petri dish, reprogram and repair the sickle cell defect. And in a mouse model, we've actually been able to show that you can affect essentially a cure in that disease. But then there's dozens of others. There are various kinds of anemias in bone marrow failure. Things called fanconees anemia, discaritosis congenitum. A variety of these conditions are all now subject to the same basic plan form. Where we take the patient's cells, we reprogram them into stem cells in a petri dish and then have a tool for research and a possible cell for therapy. | ↗ |
| 212 | Thermo Fisher Scientific | The Evolution of PSC Culture Media -- Generation of new iPSC lines wit... | 714 | 2 | | 43.2 | | 6:30 | I'm going to talk about the uses of E8 or essential aid and vitronectin to derive new IPS cells directly into these conditions. And these are some of the experimental conditions that we have used. The cell types that we used have been neonatal dermal fibroblasts from commercial vendors, adult dermal fibroblasts from commercial vendors, four skin dermal fibroblasts obtained from patient biopsy, and adult dermal fibroblasts also obtained from patient biopsies. For Plasma combination, we purchased those from adjeene. These were plasmids that were deposited by Thompson Lab into adjeene, and they're freely available. They follow the OKSM properties, and you can transform them, and you can have enough plasmids to do transfections for several years. The reprogramming methods that we have tested are the Amaxa II nuclear factor by Lanza. It comes preloaded with protocols. It's kind of the only negative thing about it. Bioregene pulser to electroparator. People may have to work out specific protocols because they do differ based on whether you're using neonatal or adult dermal fibroblasts. And then the neon transfection system, we're currently working on optimizing the efficiency for that system. Essentially, to say that you can use any system to derive your IPS cells and use E8 and V8-connect to culture them and derive your new IPS cell lines. This is our derivation scheme. I know it's a busy chart, but I just wanted to point out a few things. You can count the cells. We use about more than 1 million cells. Use the DNA that I just mentioned. Transfect the cells. You can adjust the ratio of transfected cells depending on whether they're neonatal or adult into six-well plates. Once you reach confluency, you start changing media. And then we do add sodium butyrate as a small molecule. Colonies appear between day 20 and 25. You can pick the colonies. You can culture them on vitro-nextin or metri-jell in E8. Initially, we add rock inhibitor. And then you can continue to propagate them and expand them to derive your own new IPS cells. Why sodium butyrate? The sodium butyrate is one of the small molecules. You can choose any of the small molecules that have been published and they work well. Sodium butyrate is a natural, small, fatty acid molecule. It is an H-dack inhibitor as all of you know. It significantly increases reprogramming efficiency and also increases the ratio of IPS cell colonies to total colonies by reducing the frequency of partially reprogrammed colonies. This is a big concern for the scientific community that a lot of times you will have a large number of colonies. And the ones you pick may be partially reprogrammed. There's not a lot of sophisticated testing yet without spending a lot of time and money to do that. So the favorable treatments nowadays is to use a combination of small molecules or a single small molecule to make sure that the partially reprogrammed colonies do not make it until day 25. And the beauty of this system is if you actually mark the colonies and follow them every day, the partially reprogrammed colonies will disintegrate and disappear right in front of your eyes. So it saves you a lot of time and money and aggravation because you don't end up picking a partially reprogrammed or a completely reprogrammed colonies by using small molecules. These are just some pictures. This is normal, neonatal derma fibroblast ready for transfection. These are transfected cells. It about 20 to 30 confluency. These are transfected cells at day six. And you can start seeing colony morphology appearing right in these areas. The fibroblast distinct appearance of spindle shaped cells is now changing into round looking cells. If you look at them at 10X, you can see that indeed they are different. We get about 60 to 100 colonies per 10 million transfected cells. The beauty of that is they are not partially reprogrammed. So there's a lot of colonies for you to pick from. And then the other thing which I mentioned is if you are using a skin biopsy, you can add EGF and thrombin right from the beginning, derive your fibroblast from the skin biopsy and continue your transfections. These are colonies that appear. This is day 15, day 20, day 17, day 17. Just to give you examples that the colonies are very distinct in morphology and appearance. And it is very easy to pick the colonies and start culturing them to derive IPS cells in very easy ways. These are cells that we picked and started propagating. So at 2.5, this is how they look at day 2, day 3, and day 4. And as you can see, this is a very familiar picture to all of us who do stem cell research. These do look like human blue reporting stem cells. And you can continue, you can characterize them, you can bank them, and you're ready to go. One thing that we do is while we are culturing them, we want to know whether they maintain the characteristics of blue reporting sea. So we actually use the Alkfoss live stain that life technology offers. It's a really quick and easy stain. You don't have to fix your cells, which is a very distinct advantage. The stain disseminates in two hours. So you can quickly check your colonies and move on. You don't have to dedicate plates that are fixed to do any kind of staining. And these are two colonies. They kind of have a funky shape, but you can tell that they are positive for Alkfoss. We have characterized the newly derived IPS cells for viability proliferation, blue report and sea differentiation potential by making EBS as well as carry your type. | ↗ |
| 213 | PAASE Webinars | PAASE Webinar 25: Induced Pluripotent Stem Cells (iPSC) | 659 | 19 | 1 | 43.0 | positive | 1:29:02 | No transcript | ↗ |
| 214 | MIT OpenCourseWare | 23. Stem Cells | 371786 | 6090 | 159 | 42.9 | positive | 46:19 | No transcript | ↗ |
| 215 | University of California Television (UCTV) | A Closer Look at...Stem Cells and Human Longevity | 264074 | 4541 | 151 | 42.6 | positive | 58:03 | No transcript | ↗ |
| 216 | VJDementia | iPSC models of neurodegenerative disease | 419 | 2 | | 42.6 | | 3:27 | One of the big challenges that we have faced as a field quite broadly is the difficulty in making accurate in vitro models that captured the disease process. And there are a number of reasons that that's been challenging, but potentially the biggest one is the fact that the human brain is really inaccessible to us during life. So up until the availability of IPS cells, we didn't really have a method by which we could have unlimited human neurons to grow in lab. And so in that regard, the availability of IPS has been really transformative. And so what we, what I'm saying IPS without finding it induced, who repotence themselves. Obviously, the big advantage of this is we can make specific, patient specific models, because we generate the stem cells from a sample of skin, which is easily accessible to us and non-invasive. And so in our lab, what we do is collaborate with our clinicians who are just in the building across the square. And when they see a person with either a genotypone or phenotype of interest, they ask them for a skin sample, which we can then use to make their stem cells. The next step is making the relevant cell type from both stem cells. And there are two real ways that we do that. So we can make cortical neurons as a 2D culture. And so these are cells which kind of grow in a single monolayer on plastic. We do this by a process called dual-smanned inhibition. So we're using small molecules that kind of essentially inhibit signaling pathways. And the consequence of that is the cells undergo something that very closely mimics cortical differentiation during human development. So these cells are really useful to work with. They've kind of given us a lot of insight into molecular mechanisms. They are more amenable than the 3D cultures that I will talk about in a second to things like drug screening, because obviously there's a monolayer. If we put a small compound into the media, there's a uniform exposure of those cells to that compound. However, there are some limitations. And one of the limitations of the 2D approach is of course, because we're growing the cells in a monolayer where disrupting the architecture and the structure of the cells. And so they are organized, for example, into layers like we would see the neurons organized in the brain. And so it's trying to address that. We complement our 2D models by using these 3D systems called cerebral organides. It's a very similar principle in that we are mimicking the very early stages of development of the brain. However, this time we're doing it in 3D. So these are non-adherent, they're floating cultures, probably about the size of a lentil. And as you will have seen from some of the images I used, the advantage of this talk is you get different cell types, occupying kind of different spatial regions of the organoid. They also have cost-commit limitations. I mean, in both systems, they're missing cell types such as microglia, they're missing a vasculature. And the cerebral organides tend to be a bit more variable compared to the 2D cultures which tend to be quite homogeneous. And so that's the reason that we use both approaches to complement one another. | ↗ |
| 217 | Focused Ultrasound Foundation | Cancer Immunotherapy Workshop 2021 – Focused Ultrasound Mediated Immun... | 248 | 2 | | 42.6 | | 12:21 | Hello everyone. My name is Pavlo Sanasda Sia Des from the Translational Ferributics Research Group at the University of Maryland School of Medicine. I would like to express my warmest thanks to the focused ultrasound foundation and the cancer research institute for hosting it another focused ultrasound and cancer immunotherapy workshop. I have been tasked to give an overview of the FUS immunomodulation consortium efforts. Within this consortium we explored the option of a synergistic effect between FUS and immune responses in a preclinical glioma model. This is a multi-center effort that started a couple of years ago and included six different sites across the United States and Canada. I will take a minute or two to provide background for some colleagues who may have joined recently or who may not be acquainted with the field of brain tumor biology or immunology. Each site was asked to follow the same experimental protocol in terms of tumor implantation and downstream assays. Each one of the six participating centers applied a different mode of FUS to study immune responses in this glioma-muring model. We're going to see more detail this individual modalities later in the presentation. A few words to the immune environment in the setting of glioblastoma. The glioblastoma has been extensively studied as a paradigm for cancer associated immunosuppression. Systemic immunosuppression in GBM has been demonstrated as evidence by impaired cellular immunity in patients. The glioblastomas have a positive infiltrating T-cells and harbor a relatively low number of somatic mutations compared with other solid tumor types. These tumors profoundly affect the immune system both locally and systemically. In addition to tissue resident myeloid cells or microglam, evidence suggests migrating myeloid cells have an important role in glioblastoma associated immunosuppression. The glioblastoma microenvironment is a highly immunosuppressive environment of tumor and immune cells. The lymphoid compartment also contributes to the immunomodulating environment with regulatory T-cells in particular mediating immunosuppressive effects through upregulation of various soluble factors in immune checkpoint molecules and metabolic pathways. The drug cells in the GBM tumor microenvironment can traffic by the tumor draining lymph nodes of the brain to the deep cervical lymph nodes and can present endogen to promote an adaptive endotumor immune response, although this process might be abrogated in the context of the systemic immunosuppression that is intrinsically associated with glioblastoma and can also be potentially added by the current standard of care treatments for this disease. For example, systemic thymazolamide chemotherapy induces a lymphopenia that is exacerbated by bone marrow sequenstration of T-cells. A few words to the experimental protocol in the timeline. Luciferase transduced GL261 cells were stereotyically implanted in a striatum of the brain of albino female mice six to ten weeks old. After cell implantation, tumor growth was monitored by bioluminescence and MRI imaging. On day 14 post implantation, the animals were prepared for a US treatment with one of the six modalities used in a consortium. Treatments were administered in principle under MR image guidance after core registration. On day 21 post implantation, a US treated end control mice were euthanized and their brains, spleens and cervical lymph nodes harvested for using downstream assets to assess changes in immune cell populations. This assets included flow cytometry, immunohistrochemistry and interferon gamma production. In the next slide, you are going to see the participating centers and which modality each one of these centers applied. Moving to the blood brain barrier opening modality. For a more guided focused ultrasound blood brain barrier opening, mice were catheterized for intravenous injections of MRI contrast agent and microbubbles. Mice were treated with a 1.14 megahertz spherical single element transducer within an Amar compatible FUS system after core registration. MRI contrast agent was administered intravenously to confirm tumor location by contrast enhanced T1 weighted amar imaging. A first spot grid of sonications was overlaid on the Amar visible tumor and sonications were carried out at 0.5% duty cycle for 2 minutes at 0.4 and 0.6 mega Pascal. Contrast enhanced T1 weighted amar imaging was repeated to confirm blood brain barrier opening. The combination of FUS plus microbubbles increased in treated cells maturity in the tumor, tumor draining lymph nodes and meninges. This combination also increased entaging experience PD1 expressing CD8 plus T cells in the tumor microenvironment and the percentage of CD8 plus T cells that were producing granzyme B in the superficial draining lymph nodes. Moving on to the microbascular ablation combined with blood brain barrier opening and anti PD1. Anti PD1 and body was administered in combination with FUS at 255 and 300 kilo Pascal. Although there were no effects observed at the lower FUS level, the combination of a PD1 inhibitor and FUS showed little difference to PD1 inhibitor alone for adaptive immunity. However, the combination increased activated M1 microglia in PDL1 microglia. In the spleen and a cervical lymph nodes, there was an increase in T cell immunoglobulin and I team domain receptor expression on CD3 plus and CD4 plus T cells only with a combination of FUS and checkpoint inhibitor. For thermal ablation, FUS pills were generated using a single element spherically curved air back transducer with a diameter of 25 millimeters and confoical length of 20 millimeters driven in continuous wave. The transducer had a central opening of four millimeters in diameter to facilitate hydrophone insertion. There is an unfrequency of the transducer was 1.06 megahertz but it was driven at the fifth harmonic at 5.51 megahertz to allow FUS mediated heating within the desired depth range. The gliumotumor was identified with gadolinium contrast enhanced T1 weighted in mar imaging to achieve thermal ablation and marguided focused ultrasound sonication were performed at 5.51 megahertz for 15 seconds at an acoustic power level of 2.45 watts. During sonication, a Martha momentary was performed to map the temperature rise in the brain of the focal depth of the transducer. Legion information was confirmed by assuming a conservative thermal dose threshold of 240 cumulative equivalent minutes at 43 degrees Celsius based on a Martha momentary measurements. Thermal ablation led to a slow tumor growth of 21 days post-enotulation. Finally, muonohistochemistry showed no difference in the tumor of CD4 plus and CD48 plus T cells. For pulse focused ultrasound treatments were also carried under the mar image guidance. The sonications were carried out at 1.5 megahertz and 2.3 mega Pascal. 6 to 9 spots were overlaid on the mar visible tumor and each spot was treated for 60 seconds. Regularly T cells were increased in the screen, suggesting redistribution in the cell population. In the draining lymph nodes increased in myeloid derived suppressor cells and a decrease in CD8 plus T cells were observed. In the tumor, there were no observed differences in immune cell population, 7 days post FUS. However, immunohistochemistry of tumor tissues showed increased CD plus 4 and CD8 plus T cells. For hypothermia, the tumors were located using T2 weighted MR imaging. Accurate targeting in vivo was confirmed by sonicating the tumor for 10 seconds and using a mar temperature imaging to localize the focal heating. A binary controller based on a mar temperature imaging allowed to reach the set point temperature of 41.5 Celsius within a few seconds and remained at the set temperature for a duration of 12 minutes in total at which point the treatment was concluded. FUS induced hypothermia caused changes in immune cell trafficking in brain tumors. There were significant increases in effect or CD8 plus T cells and activated natural killer cells. There were no changes observed in immune cell populations outside the brain. For histotrypcy, an 8-element transducer operating at 1 megahertz was used. The transducer had an aperture diameter of 58.6 millimeters and a focal length of 32.5 millimeters. An average of 1.5 cycle pulses were applied with a peak negative pressure of 40 megapascal were for a total of 50 pulses at a single location. Histotrypcy treatments led to a significant reduction in myeloid derived suppressor cells in the tumor and an increase in interferongamam was observed. A few closing remarks. Immunotherapy is clearly nothing short of revolutionary in the treatment of glioblastoma. Multiple findings support the hypothesis that glioblastoma is a called tumor. Glioblastomas are known to have relatively few tumor infiltrating lymphocytes compared with other tumor types suggesting that they are choiescent tumors in terms of immune reactivity. Hence, combination approaches with the aim of making these cold tumors hot and thus augmenting current immunotherapy strategies are desperately needed. The use of FUS as a local therapeutic modality to increase the availability of tumor antigens and immunotherapy to drive an anti-tumor immune response provides the rationale for this combination approach. We observed local and systemic immunologic shifts in glioma-bearing animals including both thermal and mechanical modes. This may indicate that immunotherapy combinations with FUS may be synergistic as FUS may be able to locally activate the tumor immune microenvironment to drive an anti-tumor immune response. With this, I would like to acknowledge the wonderful team that I have been fortunate to work with. In particular, I would like to acknowledge and wholeheartedly thank Kelsey Timbi, Natasha Shebani, Tyler Kerhenson, Tau Soon, Anna Staja Villalopoulou and Marc Santos. I would like to thank my mentor, Dr. Woodworth and all PIs in the consortium for their valuable support. Finally, I would like to thank again the FUS Foundation for moving the field of FUS mediated immunomodulation forward. I thank you all very much for making time to listen to this presentation. Please reach out with questions and please stay tuned as we're reaching the final stages of the manuscript preparation. I look forward to the next and hopefully to many more workshoped in future. Thank you so very much. | ↗ |
| 218 | VJHemOnc – Video Journal of Hematology & HemOnc | The role of non-antibody-based approaches to immunomodulation in multi... | 56 | 1 | | 42.6 | | 0:55 | In the world of myelomatherapies, we've seen an explosion in immune therapies, including cars and bi specifics. One of the things that I think is going to continue to be a stalwart of myeloma treatment are the non-antibody based approaches that are really dependent historically on the immunomodulatory drugs and now transitioning to the cell mods, I birdamide and mizigdamide. There are other non-antibody based approaches that can be effective. We actually have a trial running now of a simulation inhibitor that is an immune enhancer. There are other cereblon degraders that are in phase one development as well. So I think this space is ripe with a lot of different areas that can really enhance the efficacy of both unconjugated antibodies, bi specifics and CART-T cells. | ↗ |
| 219 | Boston Children's Hospital | Induced Pluripotent Stem Cells (iPSC) Part 3: The Future of Stem Cell ... | 755 | | | 42.3 | | 4:21 | We have a very high hope for being able to treat patients with the products of stem cells. I don't know when that's going to occur. I wish I could promise it as soon as five to ten years, but in reality it may take much longer. However, we're hopeful that one of the first successes will be in the blood. So we've known for many decades that we can transplant healthy bone marrow, which is the blood-forming tissue, from a donor into a diseased patient, someone who might have leukemia or might have one of these genetic diseases. The problem is that we don't have a matched donor for every patient. And so some patients go without the ability to have this potentially curative bone marrow transplant. But if we could take from every patient a skin biopsy and make their own stem cells, be able to make blood stem cells that we repair genetically and we can give them back a healthy transplant, we could solve the donor shortage problem for bone marrow transplantation, we could treat any one of dozens of diseases. Here we've gained this success with blood, we want to start expanding to other tissue types. So we now have efforts going with the lung biologists and there are very exciting opportunities for thinking about treating cystic fibrosis with this strategy. We're talking with experts in metabolic disease. We're talking with cardiologists. We're beginning to study the development of beating heart cells in the petri dish. But applications of these pluripotent stem cells are really limitless. It's been unfortunate, but already we've seen medical entrepreneurs typically not within the United States, but in rather unregulated locals like Bermuda or China or Russia, already offering so-called stem cell therapies to patients. Pants are vulnerable. Patients want to believe that there's a cure out there somewhere and they're unfortunately too easily preyed upon by the siren call of clinicians who claim to have the answers. So we're involved in trying to educate people about the realities of stem cells. Whereas we do believe we're making progress, it will take time. And so patients need to be wary. They need to use all of the resources available, including the clinicians and scientists at Children's Hospital to answer their questions. Also, we're yet children's hospital have been leaders of the International Society for Stem Cell Research. And this organization, the leading worldwide professional organization of stem cell scientists, has come up with a set of guidelines for moving this very promising science to prove in clinical therapies. And on the website, www.inscr.org, patients can find information packets to arm them with the information they need and the questions they need to have to ask their doctors whether or not the kind of therapy that they're being offered is stem cell based and is legitimate. Because we do hope to be able to have real stem cell therapies coming online over the next five to ten years. But patients have to be wary of those illegitimate folks who are promoting stem cells way ahead of their being proven. And so we hope in some day in the not-too-distant future that each area of disease, that is studied and treated in the Children's Hospital community, we'll be using in one way or another the fruits of the pluripotent stem cell biology. | ↗ |
| 220 | Boston Children's Hospital | Induced Pluripotent Stem Cells (iPSC) Part 1: Techniques for Deveopmen... | 724 | | | 42.2 | | 2:51 | We have two different types of stem cells, the traditional embryonic stem cell, which comes from early human embryos, and this new form called the induced pluripotent stem cell. By calling it pluripotent, we recognize that it has the ability to make any tissue in the body. A property that previously we thought only embryonic stem cells had. Now importantly, they're not identical, and we're still learning whether or not the induced pluripotent cells can be a full replacement for embryonic stem cells. They may one day, but certainly for the foreseeable future, we're going to move forward studying both types of stem cells. A little over two years ago, a Japanese scientist named Shinny Amanaka discovered that if you took a small set of genes, which are normally expressed in embryonic stem cells, and you made them expressed in skin cells, it would turn the skin cells into embryonic stem cells. These are the so-called IPS cells, the induced pluripotent stem cells. There's been a natural evolution in the technique itself. The practice that Shinny Amanaka introduced two and a half years ago was to carry these reprogramming genes in via viruses. The problem is that viruses insert themselves into the cells DNA and can act as mutagens, it can actually induce the cells to become cancerous. So over the last couple of years, we and others have been working on ways of eliminating the viruses from the system. And now we have a new improved approach where we can say use a virus to carry these reprogramming genes into the cell, affect the reprogramming, the reversion to the embryonic state, but then we can remove the viruses. And that's one technique that we practice that leaves us with a viral-free cell, which is a pristine cell that we can now study, and it would be a cell that would be safe to put back into a patient. The real long-term hope, though, is that we don't have to use viruses at all, that we could identify drugs which act on the same pathways as the viruses to reactivate this embryonic or pluripotent potential in every cell. Initially, we expect we'd do it in a petri dish, but maybe in the long run, we'd even be able to learn how to affect these changes or transitions and cell fate in the actual identity of a cell from one type into another in your own body. That would be cell therapy, that would be the realization of one of the great ambitions of regenerative medicine. | ↗ |
| 221 | Harvard Catalyst | Online course: Fundamentals & Applications of Clinical and Translation... | 688 | | | 42.0 | | 1:52 | We face a tremendous challenge in the 21st century. Many serious diseases and conditions remain uncured and untreated, devastating people's lives in our home communities and around the world. Researchers are uniquely qualified to find innovative solutions to this challenge. They work around the clock to discover, investigate, and deliver interventions that address these diseases and conditions. For those interested in research careers, it's critical to understand the concept of research. So where does a researcher get started? What exactly is clinical research? And how do you decide which type of research you'd like to specialize in? Harvard Catalysts Fundamentals and Applications of Clinical and Translational Research, or Factor, covers these topics and more. This 18-week online course featuring a mix of lecture videos, assessments, and resources, covers the application's spectrum of CT research, from first in human studies to healthcare interventions implemented on a population level. By the end of the course, participants are able to identify the key research methods used in CT research, including designing research studies, identifying ethical issues, communicating findings, and funding research. To learn more and register for fundamentals and applications of clinical and translational research, please visit the link below. Thank you and happy learning. | ↗ |
| 222 | The Stem Cell Doc | Best Quality Stem Cells: The Future of Regenerative Medicine - The Ste... | 72 | 1 | | 41.7 | | 1:42 | Over the last 10 years I have used a number of stem cell banks. Luckily I have come upon one that I consider one of the best in the world. I personally test the stem cells which means I take them and I send them for a third-party analysis. So I know exactly what type of product we have. This is very important. There are so many companies out there today that you don't really know what they're selling you unless somebody actually tests them. For our members, for myself, and for our patients, I make sure that all of them are the very best that we could possibly get. So over the past 30 years of practicing as a chiropractor I have always heard about the miracles of stem cells and was always curious. Curiosity eventually got to me. I am an old athlete, a football player and have had numerous surgeries from my past and have suffered along with many people for a very very long time. I decided to try stem cells just to see what it would do to me and I will tell you the results were life-changing for me. One of the most important parts about what we do is actually the handling of the stem cells. This is critical. We order them from a stem cell bank that I have been working with for over seven years and I consider them one of the best in the world. From the time they are delivered to our office on dry ice to the time we put them in a cryotank which is filled with liquid nitrogen, the handling process has to be very very specific. | ↗ |
| 223 | TEDx Talks | Advances in Regenerative Therapy:Mesenchymal stem cells | Nirupa Vyas ... | 14525 | 289 | 26 | 41.6 | neutral | 16:43 | Hello everyone, I am Nirupa Vyas and I am the co-founder and managing director of two stem cell companies, total potential cells private limited and social innovations and wellness private limited. We have been researching stem cells since 2007 for clinical applications. Now you may wonder what are stem cells and how do they work? Let me paint a picture with some examples. Picture this, wherein in a football match one of the players suddenly gets injured on the field. The sports medicine doctor makes a diagnosis of an anterior cruciate ligament tear. This is followed up by a surgery to repair the tear. After that it takes weeks of healing and months of physiotherapy and physical rehabilitation before the player actually gets back to the field. Or a tennis player or a cricket player suddenly develops a tennis elbow pain and has to take time out from the court. He or she may have to resort to steroid injections to resolve this pain. Another situation where a 45 year old office goal gets debilitating leaping. It is diagnosed as second stage osteoarthritis. The advice that is given by mainstream medicine is to get a knee replacement done. Doesn't matter that the life of the implant may be only 15 years and a revision surgery may be required after that. Finally think of a 75 year old grandparent who gets diagnosed with Parkinson's disease. They are put on medication which will have to be taken for a lifetime. All that can be done is to manage symptoms but this will not cure or reverse the disease. The classic scenario for all these conditions would be to give multiple drugs and surgical interventions. But with the advances in regenerative therapy all these conditions have been helped with the help of meez and kymal stem cells which is done at our labs. When regenerative therapy is opted for the football player with the ACL injury would have stem cells injected from his or her own bone marrow which would help repair regenerate and renew the cartilage much faster. This would enable the player to return to the field much faster and cut back on medical expenses. The tennis player gets an injection of a dose of stem cells made out of his own bone marrow at the site of the pain and his pain is gone. The 45 year old is given two stem cell injections into the knee made out of their own adipose tissue which will help regenerate the worn out cartilage. The natural joint is and the person gets 5 to 7 years to do physiotherapy and physical rehabilitation to push back the knee replacement surgery. The same process can be repeated the stem cell therapy can be repeated after 5 to 7 years if the pain starts again again pushing back the knee of the knee replacement. The grandparent who was diagnosed with Parkinson's disease can be given stem cells from their own bone marrow into their spine thus delaying the onset of the disease and maintaining the quality of life. These are just some of the uses of meez and kymal stem cells in regenerative therapy. What is regenerative therapy? Let us just elaborate this term a little further. Regenerative therapy is the therapeutic application of stem cells based on their potential to stimulate repair mechanisms and restored function in damaged body tissues or organs. Regenerative therapy utilizes human cells and tissue products. So the example is stem cell therapy platelet rich plasma therapy to name a few. The human cell tissue product secret compounds called growth factors and cytokines that aid in treatment with chronic and degenerative diseases. This therapy stimulates natural healing process by stimulating the reparative response to aging, diseased, dysfunctional or injured cellular tissue. Some of the relief to the symptoms is immediate. The inflammation is cut down and the pain is gone. But some will the process of regeneration takes the investment of time depending on the damage and the immune system of the person. Let us understand what are stem cells and how do they work. Stem cells are unspecialized cells in our body that can differentiate into various cell types and thus can help the process of regeneration. They have a property of angiogenesis that is they are capable of forming new blood vessels. They are anti-inflammatory and antimicrobial in nature. They also have the property of immunomodulation that is they can modify the body's immune response. And lastly, they stimulate regeneration at the site of the damaged or injured tissue. So they are capable to repair, regenerate and renew damaged tissues or organs. Now let us take a deep dive into what are mesenchymal stem cells. The definition of mesenchymal stem cells is that they are multi-portant stromal cells that can differentiate into a variety of line-ages. That is they have the ability to differentiate into cell types of different germ layers. That is the ectoderm that's the skin, mesoderm, the bones and the cartilage and endoderm, the organs. Stem cells derived from the ectoderm for example that is the skin can translate to form neural cells in the brain. So this phenomenon is referred to as cell trans differentiation or plasticity. Mesenchymal stem cells are immunonive. That means a person's immune response will not reject the mesenchymal stem cell transplant. Thus this therapy can reach a number of people. There are various sources of mesenchymal stem cells. The bone marrow derived mesenchymal stem cells are most commonly used and well researched. Addipous tissue of fat provides a more abundant and easily accessible source of stem cells. Ambelical cord blood, ambelical cord that's the vortngel and placenta are also rich sources of stem cells. The autologous cells are defined as the cells that come from a person's own body and allogenic cells come from a donor tissue. So bone marrow, adipose tissue, menstrual blood, dental pulp all fall under autologous sources. Ambelical cord, cord blood, placenta are the allogenic sources. I can safely point out that many of the children who are sitting in the audience would have had their cord blood and cord tissues saved. In a private cord blood bank, so in case at the time of the birth, if there was a complication, these tissues would have come in very handy for the child. Typically if the child is not crossing milestones, the pediatrician or stem cell clinic will advise injecting the stored cord blood to achieve normalcy. But the parents and grandparents don't have that tissues stored and that is where autologous regenerative therapy is very convenient wherein their own tissues can be taken and processed in the lab and re-injected back at the damaged area to regenerate the damaged tissues. So if anyone of you requires stem cell therapy, all that you need to do is to look inside your body. So, Mies and Kamil's stem cells find a lot of clinical applications in regenerative therapy. These we have been working since 2007. In the laboratory that we have set up to work on stem cells, we were granted a clinical trial by Department of Biotechnology, Government of India. The trial was to study adipose derived stromal vascular faction for the treatment of arthritis of the knee, that is osteoarthritis. 25 patients were selected for the clinical trial who had grade 2 to grade 4 osteoarthritis. The lab process was carried out at our GMP Class 5 facility. The process of harvesting the stem cells has many steps. First, the plastic surgeon takes the patient into the operation theatre and with specialized cannulas, the belly fat is taken out. This is known as lipo aspirate and the process is known as lipo aspiration. This tissue is then moved back to our lab where the cells are harvested and a sufficient number of cells are brought out for treatment. Finally, the Mies and Kamil's stem cell dose travels back to the operation theatre where the patient is and a qualified orthopedic surgeon will give intraarticular injections straight into the knee. Following criteria were evaluated to study the success of the therapy. First was the range of motion. There was an improvement of knee society score for range of motion criteria in all the patients after 12 months, then the pre-treatment. The pain was reduced, the walking score was improved, climbing of the stairs improved then from the pre-treatment. There is a visual analogue score which talks about which is subjective but it is highly indicative of the patient's satisfaction. At the end of year 1, 24 out of 25 patients scored between 9 to 10. So to stem it, sum it up, it establishes the safety and the efficacy of the adipose derived Mies and Kamil's stem cells for the treatment of osteoarthritis of the knee. The study has been published and we have been awarded a process patent. I would like to describe my own journey with stem cell therapy. I had a ligament tear which impacted all my mobility and I couldn't even walk properly. A surgery was advised which I did not want to undergo. I was given three rounds of stem cell therapy over a period of four years. With constant physiotherapy and physical rehabilitation, I have been able to regain 95% of my joint health and movements. Other uses are for neurological conditions. Research suggests that stem cells have neuro protective effects which can help for treatment like Alzheimer's and Parkinson's diseases. By promoting neural repair and reducing neuro inflammation, Mies and Kamil's stem cells could help preserve cognitive function as we age. Children with cerebral palsy are being given injections of stem cells into their spinal cord and ample scientific data has been generated to show that the children start crossing the milestones after receiving stem cell therapy. During COVID, patients were given high doses of steroids to bring down the inflammation in the bodies. This subsequently developed a vascular necrosis of the hip that is they would require a hip replacement to be done. 19-year-old, 20-year-old young adults were being advised to do hip replacement. Here, autologous cell therapy using stem cells from the bone marrow were injected in their hip joints and the hip replacements was avoided and they had good results. Mies and Kamil's stem cells are also being used for anti-aging therapies. So, as we age, our cells accumulate damage and they enter into a state of senescence, wherein they no longer divide or function properly. The MSCs have been shown to secret growth factors that can reduce cellular senescence and promote the regeneration of the diseases. Chronic inflammation is a hallmark of aging and is linked to many age-related diseases. So, the stem cells, the Mies and Kamil's stem cells possess strong anti-inflammatory properties which can help reduce the inflammation. Other applications in anti-aging are for the rejuvenation of the skin and hair. Plastic surgeons and dermatologists aspirate the belly fat out of which we make nano fat and micro fat, which is rich in stem cells and in growth factors. This is being used in place of dermal fillers and Botox. It improves the skin elasticity, reduces the wrinkles, it promotes a more youthful appearance by stimulating the collagen production. Hair fall and hair thinning is affecting youths to adults. So, Mies and Kamil's stem cells along with platelet rich plasma is given in the hair follicles. It is injected into the scalp in the hair follicles to stimulate and regenerate the follicles to achieve hair growth. The images that you see are the images of my 19-year-old son who started getting a balding patch. Mies along with PRP were injected in his spot and in six months we had results that the entire balding patch was gone. There are challenges to the Mies and Kamil's stem cell therapy. Different laboratories use different protocols which can result in varying cell quality and potency. So, it is very important that standardized procedures need to be developed which will help ensure consistency across treatments. The production and administration of Mies and Kamil's stem cell therapies is expensive so it doesn't reach the masses. Lifestyle modifications are very important to the success of stem cell therapy. A smoker or drinker cannot expect any results out of stem cells if they do not quit their smoking and drinking. So, what I leave you all with is that the next time around, someone near you needs some medical treatment. Please do research whether stem cell therapy can be an answer to that and definitely do ask your doctor about it. When all of you sitting here in the very near future, pick careers, research in the field of stem cells is an exciting proposition and I request you all to definitely apply your minds to it. Thank you very much. | ↗ |
| 224 | UCL EGA Institute for Women's Health | Pascale Guillot, Cellular Reprogramming and Perinatal Therapy | 561 | | | 41.5 | | 0:59 | My name is Basque Anguio and I'm a senior lecturer at the UCN Institute for Women's Health and I live in research team that is interested in cellular programming and stem sensor happy. Almost important findings of form was the recent discovery that it is possible to revert human cells back to full purreportance using chemicals alone. These cells are called chemical inidious purreportance and sensor of chemical appearance. We derive appears from human-feet of cells found in the ametive feed or placenta during gestation. We then derive specific inidious and inject them in material or at birth to treat brittle body disease or the uniterbreum age. | ↗ |
| 225 | ANCHORS AND EAGLES PODCAST | Longevity & Stem Cells: A Deep Dive #shorts | 84 | | | 41.5 | | 0:37 | I was able, you know, I talk about a lot of stem cells stuff. What you get guys don't understand is a lot of these stuff I really like enjoy is stuff about longevity. I'm very, I don't know if it's because of my age. I always thought that by the time I be at this age, they'd have a curious for a lot of things. Well, it's amazing is at this age, there's so much stuff coming out right now. There is stuff about a curious from cancer and longevity, but David Sinclair has been, someone that I followed a little bit, but this week I got to talk to somebody that's actually working on stem cells here in Florida. | ↗ |
| 226 | Dr Aiden Core | Senior Health | SENIORS: Add THIS to Your Coffee — Stem Cells Reactivate, Cancer Starv... | 81 | 9 | | 41.5 | | 28:18 | No transcript | ↗ |
| 227 | Delora OBrien - Off the Cuff | [SPECIAL BROADCAST] Stem Cells: What's All the Fuss About? | 1129 | | 26 | 41.3 | neutral | 1:03:25 | No transcript | ↗ |
| 228 | American Thoracic Society | Understanding Epigenetic Reprogramming in COPD: A Breakthrough Study R... | 1236 | | 1 | 41.0 | neutral | 2:32 | [Music] welcome to Red in motion our video will look at an important paper in the American Journal of respiratory cell and molecular biology here we discuss epigenetic reprogramming drives epithelial disruption in chronic obstructive pulmonary disease by researchers from Johns Hopkins and other collaborating sites in America chronic obstructive pulmonary disease COPD remains a PR Global health issue contributing significantly to mortality and morbidity worldwide despite its profound impact there has been a notable lack of focus on addressing epithelial alterations which play a critical role in the disease process Recent research has revealed that loss of cell cell adhesion molecule e caterin encoded by the cdh1 gene in different types of lung epithelial cells causes chronic airspace enlargement and Airway hyperactivity in mice understanding whether cdh1 plays a role in COPD is essential for developing targeted interventions that can alter disease progression and improve patient outcomes to this end researchers explored the role of DNA methylation in the regulation of the cdh1 Gene and its implications for epithelial Integrity in COPD by utilizing differentiated normal and COPD derived human Airway epithelial cells genetically manipulated Mouse tral epithelial cells and precision cut lung tissue sections the researchers observed a significant increase in DNA methylation at the cdh1 enhancer D region in COPD derived cells this heightened methylation correlated with reduced binding of RNA polymerase 2 the multiprotein enzyme complex that is vital for Gene transcription they also found that treatment with the DNA demethylation agent 5 ASA 29 deoxy citadine resulted in restored epithelial Integrity reducing airspace enlargement in COPD affected tissue these findings highlight a novel mechanism targeting epigenetic modifications to counter tissue remodeling in COPD affected lungs and offer a promising Avenue for developing Advanced therapies for more details please read the article by Dr Bonnie H junglu and colleagues thank you for watching red in motion | ↗ |
| 229 | VJHemOnc – Video Journal of Hematology & HemOnc | Immunomodulation and the microbiota | 259 | 1 | | 41.0 | | 1:22 | So we live in symbiosis with billions of microorganisms and this is also a growing field in which we try and investigators try to understand how these microorganisms and their relative proportions will affect the functions of our immune systems and how we could eventually use this knowledge to induce better response, a sport of allogenic transplantation, a sport of corticells. There was a very nice presentation at the opening ceremony by a young investigator from the Memorial Sloan-Kitrin Cancer Center in New York demonstrating that actually there is a relation between the composition of the microbiota and response to corticells. So we can close the loop at some point. We are acting on the immune system. Our microbiota is also responsible in many aspects for the activity of our immune system and response to immune modulation, whatever its nature. | ↗ |
| 230 | VJHemOnc – Video Journal of Hematology & HemOnc | ECP immunomodulation for cutaneous lymphoma: current & future perspect... | 259 | 1 | | 41.0 | | 1:04 | For patients with a Rithroidermic, my case is fungories or says we syndrome and that's the condition where they're read all over. One of our early treatments that we choose is ECP or photophoresis. This was actually introduced by Rick Edelsson way back in the 1980s when he used to use phototherapy or poover for the skin and he thought hang on, for these patients how about treating their blood because they have normal cells in their blood. So really then, photophoresis was born and since then it's gone under several changes. The latest machine is a select machine which has been available since 2009 and effectively treats patients with a Rithroidermic MF and says we syndrome. It has a much quicker treatment time so patients can be now treated within an hour and is effective in about 60% of our patients which is similar throughout the world. | ↗ |
| 231 | Queen's Health Sciences | Translational Institute of Medicine (TIME) | Research at Queen's Unive... | 253 | 1 | | 41.0 | | 3:54 | Translational medicine is a way of performing science and a way of performing medicine. It basically takes the problem of the patient at the bedside and moves it to the basic science research lab. And in fact it goes in both directions. So you have clinicians who look after patients asking questions and having basic scientists help answer those questions. And you have basic scientists who have observations about disease who are working with patients and patient material to find solutions and cures. So time is an acronym for the Translational Institute of Medicine. And this is our new Progressive Virtual Research Institute. And the goals here are to bring together the expertise of scientists within the Department of Medicine and across the faculty and the university itself to enable us to follow our research questions at the highest level. There are three components to time that really need to be drawn out. Firstly, we're interested in bringing world class state-of-the-art research. Secondly, we're very interested in education. And as a result we have the team ed program which is bringing a new generation of translational scientists to the world. Thirdly, we have the time network. And the time network is important because it captures the breadth of translational research that already exists at Queen's University. Queen's needs time and indeed any university needs time because resources are precious. This is a small university and we aspire to become a leading research intensive university not only in Canada but in the world. Time captures what already exists and gives it an aim and allows strategic development to ensure that translational medicine is a priority for the research community that's already here. Time helps translational medicine at Queen's and that it brings it to life through trainees, infrastructure and connectivity. The depth of a scientist is to be left alone in their lab with no partners, no resources. In contrast, vibrancy is breed into a lab when there are lots of partners. Time has already made tremendous successes in its very early history. It's brought together over 200 research scientists in the university and it's also created a large number of state-of-the-art research platforms that cut across many disciplines and have allowed a very rich research environment for all of its members. The team Ed Corses run by Dr. Paula James selects from a very talented field of masters and PhD candidates, brings them into the lab, teaches them through interesting courses in which they interact with patients. Time has allowed incubator grants which have facilitated not just individual translational researchers but teams of researchers that across disciplinary to apply for funds to be able to address the most important translational questions. I think the future of time will likely include future CFI applications. It will also involve the university growing in terms of the number of CHR and Tri-Council funded researchers that we can attract and retain at Queen's University. I think these are all results of having an enterprise-like time. At the end of the day our ultimate goal is to bring new therapies and treatments for our patients and this seems to be a very achievable goal. | ↗ |
| 232 | AHJAlternativeMeds | Stem Cell Reprogramming | 220 | 1 | | 40.9 | | 4:08 | How does one cell, known as a stem cell, give rise to millions of cells? And how do they come to be organized into complete structures, such as limbs, a heart, or a brain? Dr. Juan Carlos Belmonte, a professor in the gene expression laboratory of the Sauk Institute in La Jolla, is researching how these stem cells work. The very first days after a male and a female cell get together, you form an embryo. And inside the embryo, the very first few cells, these are what we call embryonic stem cells, because they come from the embryo. And they make all the different cell types of our body, which we have around 250 different cell types. They come from these stem cells, so they can become anything in vivo and they do so. And the idea is that how can we educate that process outside of the embryo, in vitro, how can we can educate any cell type to become any other cell type? We asked Dr. Belmonte, what is stem cell reprogramming? To say in other words, is to convert one cell into another cell type. To program that cell again to do something different. And that's one of the goals of regenerative medicine to produce cells, to restore other cells that are gone. They don't work normally. And one way to obtain these cells is through convert one cell type into another reprogramming them. To make a hair cell become a liver cell, or to make a heart cell become a neuron. Just convert one cell into another reprogrammed their genetic machinery to make a different cell type. But imagine that our hair is not healthy, that somehow has a disease, that the disease is general. Or the cell we start with, the heart, or the skin, or the pancreas, you have diabetes. You don't start with a healthy cell. So you first need to make that cell be normal, a healthy cell, and then reprogrammed or reeducated that cell to become a stem cell. So that's an experiment we did a few months ago. We started with a hair from a patient that had a disease, and we obtained blood at different cell type, but not anymore with the disease. That proves that you can manipulate, which has a few genes, how a cell can become another cell type. The major problem now, okay, that's great. So now you could put these cells, the blood cells you have generated into the patient, and try to alleviate the problem the patient has. So the major bottleneck that the field has right now, I would say, is that in this process of reprogrammed the cell, we are generating a cell with the potential to induce tumors. And therefore, until we don't have a better knowledge and handle how to avoid that problem, this technology will not progress too much into the clinical application. Instead of trying to educate the cell to become a very primitive embryonic stem cell, and then educate back again to be whatever. With the caveat, we generate cancer, the idea could be just to differentiate then a little bit, figure it then just one step, and then do the particular tissue we are interested on. So that would be another avenue to work towards regeneration in general. | ↗ |
| 233 | UMC Utrecht | Eureka International Certificate Course on Translational Medicine - Si... | 220 | 1 | | 40.9 | | 3:22 | We are entering a completely new phase in medicine and we are completely unprepared to do so. Eureka is helping young teletr researchers to be prepared. Already I feel like I'm becoming more savvy about the things that I need to know. Each piece is kind of a new perspective for me and I really have appreciated that already. The faculty bring with us a whole set of contacts and networks that are beyond ourselves as well that we can connect our students with. And they get a network of their peers who are now advancing in the field. And so that's really important. We're helping navigate through the complexity of all these things and career advancement. The program has given me a really broad and international perspective on my work and showing me that there is an international community if people like me, you are doing translational sciences, clinician scientists. We try to provide the fundamentals or at least a view of the fundamentals and the pathway. But also add things that are really at the edge now and are going to shape translational medicine going forward. What it was focused on was learning how to think about translational medicine and the translational process and learning how to think about how to do the work in ways that usually not tough. I just love that they walk away energized to go back into their environment, moving into a new place and thinking slightly differently about their role in translational medicine. This course really helped me to also weigh the advantages and disadvantages of all different options and directs me towards better understanding of where I should go. Our participants actually learn new insights that you don't learn in your normal medical school about what different translational medicine actually can make. What I'll come back with is information that I didn't even know that I was missing and I think that isn't something that you would typically learn from books or journals or through the regular sources. At the end of the course, these young physician scientists will go back to their institution and say, I'm different, but I'm very valuable and I do something unique. At the end, the purpose is really to advance medicine to the benefit of the patients. I've met such a diverse group of people with such diverse backgrounds, but inherently with a passion and an enthusiasm to take things that we've learnt here and make an impact in human health and disease. | ↗ |
| 234 | Dr Monica Kieu | choosing which way to apply PRP, PRF, EZ gel, exosomes, and stem cells... | 66 | | | 40.9 | | 1:12 | I've done a ton of videos about PRP, PRF, EZGEL, exosomes, or stem cells in the past. There's two main ways I would use them either topically as a serum when microneedling or injected. And there's different rationale for using each method, so let me explain. When you're injecting the product, you're either going into the deep dermal layer or even below that in the subcutaneous layers. This allows a targeted and concentrated delivery to the areas of concern. When applied topically, you're just getting into that epidermal layer, maybe in the top layers of the dermis. Injections allow for more potency and efficacy, because you're getting higher bioavailability of the product. When applied topically, you may get some degradation of whatever it is you're using. Injection is incredible for volume loss, hair restoration, fine lines and wrinkles, deeper acne scars. While topical is good for just global skin improvement, think better skin texture, improvement in pigment, they can make your pores look smaller. I often combine these techniques together. For example, I might inject PRF to the under eyes and the temples and follow up with micro-needling to improve the overall skin quality. | ↗ |
| 235 | Centre for Eye Research Australia | CERA | CERA's cellular reprogramming research – Dr Raymond Wong | 181 | 1 | | 40.8 | | 1:29 | the retina is a thin layer of cells at the back of the eye it's responsible for detecting the light that we see and converting it into electrical signal sending it to the brain to interpret it as an image my lab looks at using stem cell technology to regenerate the retina and hopefully we can utilize that to help patients restore their vision a typical day usually include working in a lab with human cells grown in the dish and we store them in an incubator that allowed us to test our technology and develop new treatment using this modeling we can use stem cell technology to develop human cell culture that we can start growing in the lab and that provides a resource for us to work with them and understand what's wrong with them in order to develop a new treatment options to help the patients the major motivation for me is the potential of our research to really help patients with vision impairment to improve their life quality and improve their vision i think that really is the key for me every day waking up knowing that i should be working hard in order to progress the research because we do have a potential to make a difference to the patients and really help their life [Music] you | ↗ |
| 236 | Comunicación Fundación Progreso y Salud | Andalusian Cellular Reprogramming Laboratory, LARCEL (english version) | 320 | | | 40.0 | | 5:21 | The Andalusian Cellular Reprogramming Laboratory, La Thalle, is a research space exclusively devoted to the study of cellular reprogramming techniques, born as a result of the alliance between the Ministry of Health of the Andalusian Regional Government and the Michigan State University and the US. La Thalle is embedded in the framework of the Andalusian Initiative for Advanced Therapies. Its objectives include developing new therapies by means of research in new technologies with application into regenerative medicine as an innovative feature of medical care and progress in Andalusia. A pioneering technique. Cellular Reprogramming involves modifying the characteristics and functions of an individual's adult cell. It entails a regression of its evolutionary development to generate blurri potent stem cells, capable of giving rise to any type of tissue or organ and turning it into a different type of cell without the need to transform it into an intermediate blurri potent cell. In the future, this set of techniques will make it possible for a skin or bone marrow cell, for example, to become a neuron or any of the more than 200 cell types that make up the body of an adult individual. In other words, through cellular reprogramming, the memory of a cell's development can be erased, subsequently inducing the cell to take on new identities, including types of cells affected by illnesses suffered by the patients donating the original cells. Andalusian and US researchers work jointly at this laboratory by virtue of the agreement between the Andalusian Ministry of Health and the American University that will further more share the results obtained from the research carried out in the context of this project. The entire professional team is under the supervision of Professor Jose Thibeli, Associate Scientific Director of the Andalusian Initiative for Advanced Therapies and Director of the Cellular We Programming Laboratory of Michigan State University. Facilities and Equipment La Thel, the Ministry of Health's ambitious research project with International Dimension is based at the Cartouche Science and Technology Park in Seville, and occupies a surface area of more than 400 square meters distributed over two floors. The studies carried out at these installations, which encompass basic as well as applied research, have an enormous potential value for opening up new paths in the field of cell therapy and regenerative medicine. The laboratory comprises of state of the art equipment to carry out quality research and to achieve results that are hoped to respond to citizens' health needs. This equipment is at the service of the World Research Community for generating human reprogrammed cells and applying them in clinical trials. La Thel has been designed with the aim of creating open plan spaces that favour interactions between professionals and methods of work based on cooperation and interdisciplinarity. It has an 85 square meters GMP laboratory to allow the transfer of basic research, the clinical research through the production of cells following quality standards to be applied to patients. There is also a molecular biology laboratory with different work zones to be used among other things for the extraction, handling and analysis of DNA and RNA samples or gene cloning. And cell culture laboratories divided into separate rooms for human cell cultures and animal cell cultures, mouse and zebrafish, and designed for the study of cellular reprogramming techniques in sterile conditions. The laboratory also has an imaging room with microscope and digital image acquisition equipment, a histology room for obtaining and handling histology samples in suitable conditions, and a zebrafish animal facility designed for keeping specimens of this typology to be used as animal models for understanding cellular reprogramming mechanisms. La Thel unquestionably embodies the spirit of health research, development and innovation and also represents the will to grow and advance in new research in the context of cellular therapy and regenerative medicine in a way that directly benefits the population by improving its health. La Thel re-programming tomorrow's health. | ↗ |
| 237 | TEDx Talks | Stem cell therapy -- beyond the headlines: Timothy Henry at TEDxGrandF... | 243320 | 1999 | 219 | 39.9 | positive | 17:54 | No transcript | ↗ |
| 238 | Health Tips & Secrets | 7 FOODS | INCREASE STEM CELLS IN 30 DAYS | REVERSE AGING NATURALLY | 43 | | | 39.8 | | 9:03 | Imagine waking up every single morning knowing your body is literally regenerating itself from the inside out. Your organs repairing, your joints rebuilding, your brain fog lifting, and your skin aging in reverse. What if I told you that you possess an internal superpower, a biological fountain of youth that most people completely ignore, and what if I told you that by simply changing what's in your refrigerator, you could double the activity of that superpower in just 30 days. Today, we aren't just talking about healthy eating. We are talking about hacking your body's master repair system. We are talking about stem cells, and the research coming out of Harvard and the National Institutes of Health is so shocking that it changes everything we thought we knew about aging. Stick with me. Because Food Number 4 on this list actually activates a specific longevity pathway that pharmaceutical companies are spending billions trying to replicate. Let me introduce you to a guy named Mark. Mark is 52. He used to be an athlete, but lately, he feels like his body is betraying him. A simple weekend hike takes three days to recover from. A small cut on his finger takes forever to heal. He's tired, he's gaining weight, and he just assumes this is normal aging. We've all felt like Mark, right? That creeping feeling that the warranty on your body has expired. But here's the truth that the multi-billion dollar anti-aging industry doesn't want you to know. Your body was designed to heal itself. The science, simple, and exciting, deep inside your bone marrow. There is a sleeping army. These are your stem cells. Think of them as your body's blank slate repairman. When you get injured, when a cell dies, or when tissue degrades, your body sends out a chemical signal, an SOS, and these stem cells wake up. They travel through your bloodstream to the site of damage, and then they transform into whatever cell is needed. Liver cell, skin cell, brain cell, they can do it. Your body is a regeneration machine. But here is the terrifying part that the nature journal and stem cell research and therapy have documented. As we age, this army shrinks and falls asleep. By the time you're 50, the number and vitality of your circulating stem cells can be a fraction of what they were in your 20s. We blame aging on wrinkles and gray hair, but true aging is simply the loss of regeneration. We aren't dying of old age. We are dying of a repair deficiency. The problem, modern lifestyle. Why do our stem cells retire early? Because we are living in a war zone. The standard American diet, ultra processed foods, liquid sugar, and seed oils creates chronic inflammation. It's like throwing water on your body's internal fire. High sugar spikes insulin, which is a direct signal to your stem cells to stop working. Add in chronic stress and lack of sleep. And you are bathing your bone marrow in cortisol. A hormone that literally suppresses stem cell activity. We are living in a way that keeps our own repair system handcuffed in the closet. But we can flip the switch. We can send out the signal to wake the army. The solution, seven powerhouse foods. This is the good part. Food is not just fuel. It's biological information. It's data and certain foods tell your body. It's time to regenerate food number one, green tea. Specifically, the compound EGCG. Researchers have found that EGCG is a powerful protector of stem cells. It doesn't just wake them up. It shields them from the oxidative stress that would otherwise destroy them. Think of it as armor for your repairman. Drink it daily. Food number two. Blueberries. But not just for the antioxidants. Blueberries contain a compound called taro still being. Studies show this little molecule can actually cross the blood brain barrier and stimulate stem cell activity in the hippocampus, the memory center of your brain. We aren't just healing muscles here. We are regenerating the mind. Food number three. Fatty fish. Salmon sardines macro. They are packed with omega. Three fatty acids. A groundbreaking study showed that omega, 3S, actually increased the number of hematopoetic stem cells. The mother cells that create your entire blood and immune system. More omega. 3S equals a stronger, more resilient immune army. Food number four. And this one shocked researchers. Pomegranate. There's a compound in pomegranates called urelithin A. Listen to this. Your cells have little garbage disposals inside them called mitochondria. As we age, these disposals get clogged. Urelithin A actually recycles the old broken mitochondria and triggers the growth of new healthy ones. A process called mitophagy. By clearing out the cellular junk, you create a clean fertile environment for stem cells to thrive. This is true cellular regeneration. How to eat it? Drink the juice, no sugar added. Or eat the seeds like their candy. Food number five. Turmeric. The golden spice. Curcumin. It's active compound. Is one of the most studied anti-inflammatory agents on the planet. By lowering systemic inflammation, you are essentially putting out the fire in your tissues. You are stopping the noise so your stem cells can hear the signals to start repairing. Always eat it with black pepper to boost absorption. Food number six. Dark chocolate. Yes. You heard me. Over 70% cocoa. It's rich in a compound called epicatechin, which in studies has been shown to boost stem cell mobilization. Similar to exercise. It helps your vascular system. Ensuring those stem cells have a highway to drive on to get to the damage. Food number seven. Broccoli sprouts. These little things are the most concentrated source of sulforophane. This compound is a master switch for detoxification. It tells your liver to ramp up cleaning. Reducing the toxic burden on your body. When your internal environment is clean, your stem cells don't have to work in a toxic dump. They can focus on building. The three zero day routine. So how do we stack these for maximum impact? Here is your simple three zero day activation protocol. Morning. Start your day with hot water and lemon. But 30 minutes later, have a cup of green tea. For breakfast, throw blueberries and spinach, which is high in full late, great for cellular division into a smoothie afternoon. For lunch, have a salad with broccoli sprouts and a dressing with turmeric and black pepper. For a snack, have a square of dark chocolate and a handful of walnuts. Another great source of omega. Three S. Dinner. Eat fatty fish like salmon three times a week. And for dessert. Have a bowl of pomegranate seeds. This isn't a diet. It's a data stream. You are feeding your bone marrow the specific instructions to rebuild. Addressing. Skepticism. Now, I want to be straight with you. This doesn't mean eating a pomegranate will magically give you a new liver by next Tuesday. This is biology. Not magic. But the research from institutions like the National Institutes of Health confirms that these nutrients create the optimal physiological environment for stem cell proliferation and differentiation. You are removing the barriers and providing the tools. If you want to double your stem cell activity, you have to stop poisoning the well and start filling it with clean water. Imagine 30 days from now. You wake up and you don't feel that morning stiffness. You cut yourself shaving. And it's gone by the next day. You have the energy to play with your kids or grandkids without needing a nap. You aren't just surviving. You are regenerating. You are tapping into the ancient code written into your DNA. This is regenerative health. This is how we take back control. I want to know which of these foods you already eat every day. Is it the dark chocolate? Or are you a blueberry person? Comment, team blue, or team dark below. Let's get a conversation going. If you want more science-backed secrets to unlock your body's potential, hit that subscribe button right now. And seriously, share this video with someone who needs to feel young again. It might just change their life. I'll see you in the next video. | ↗ |
| 239 | Novartis Careers | Meet Michelle - an expert in Translational Medicine at Novartis | 285 | | | 39.7 | | 2:01 | So our stories always start with our ancestors and our childhood. And my father's a big reason that I'm in this field today because he always encouraged me to be a doctor. And my father was born in Malaysia in 1935 and he used to go to school through a rainforest. When he was 10 years old, he lived through World War II, during which he witnessed many acts of violence that later came back to haunting. He then was awarded a British Commonwealth Scholarship and he went to London to study nursing and there he met my mother and she was escaping Salazar's dictatorship of her home country Portugal. And so they started a new life together and when I was four years old, the pressures of work plus the early abuse and war trauma that my father had experienced, they all led him to a complete breakdown. That meant he was unable to work and I remember at that time, waking up hearing him screaming in the middle of the night through nightmares. Eventually he emerged and he was able to find self acceptance and peace in his later years. And my own destiny unfolded. I did train as a doctor and I became a pediatrician in the British National Health Service where I worked for 10 years. I made the jump to move to Switzerland and joined industry and started working in rare diseases which has become my passion. I wanted to share my story and where my father started in his life and how that inspired me and allowed me to make the journey to be here today. So that was important to me. If you want to work for an organisation that really supports you to make the greatest contribution that you can, then consider joining us here at Noatis. | ↗ |
| 240 | BU CTSI | Reprogramming: Induced Pluripotent Stem Cells, Concepts, and Methods f... | 2909 | 56 | 5 | 39.6 | positive | 53:07 | No transcript | ↗ |
| 241 | Boston Children's Hospital | Induced Pluripotent Stem Cells (iPSC) Part 4: Continued Research | 234 | | | 39.2 | | 2:55 | Operating under restrictive policy for the last eight years certainly has encouraged a degree of outside the box, thinking. To every cloud there's a silver lining and I hesitate to say that the president's restrictions were responsible for these breakthroughs in direct cell reprogramming but no doubt this major breakthrough has in fact emerged in a setting where we were otherwise compromised in the types of science we could do with embryonic cells. But it's important to realize that the breakthroughs in direct cell reprogramming are built upon the foundation of embryonic stem cell biology. The new induced pluripotence stem cells, the ones where we can make any patient skin cells back into an embryonic like state is very exciting but it doesn't answer all of our questions in science. The embryonic stem cells remain the gold standard. We've studied them in mice for 30 years in humans for 10. We've only had the induced pluripotence cells for two years so we have much less experience. We are certainly hopeful that they'll do everything that we know the embryonic stem cells can do but we remain to prove that point. There are also many very important questions that relate to the earliest stages of human development. These are questions that are absolutely germane to issues like birth defects, human fertility and infertility and some kinds of cancer. We'll never get at those questions by studying reprogrammed skin cells. We need to go to the early human embryo to be able to understand those issues. The liberalization of federal funding under the new Obama plan will be exciting and will offer us more support for carrying this vision forward but it won't provide us all the resources that we need. Unfortunately, the National Institutes of Health isn't particularly effective at funding this very risky translation of bench research to the bedside and there are lots of resources that we still need to go to the philanthropic community to fulfill. So with a combination of this enhanced federal support and the visionary support of philanthropists we hope to be able to put together the very, very considerable sums of money. It's going to take us to realize this goal, this $60 million, seven year goal of getting stem cells into patients. | ↗ |
| 242 | University of California Television (UCTV) | Understanding Human Pluripotent Stem Cell States and Their Application... | 38265 | 591 | 13 | 39.0 | positive | 58:11 | No transcript | ↗ |
| 243 | EuroGCT and EuroStemCell | Stem cells - the future: an introduction to iPS cells | 238839 | 2058 | | 38.4 | | 16:43 | One of the most extraordinary scientific discoveries of this century was made by a doctor-turned-scientist working in Japan. Shina Yamanaka had been involved in the field of stem cells for ten years. When his experiments changed the way we understand human biology. Shina Yamanaka is a medical doctor and a scientist. He was interested in finding a way to treat incurable spinal cord injury patients. I was an orthopedic surgeon, so I didn't do any stem cell research at that time. It was like twenty years ago. But I had many difficult patients suffering from spinal cord injuries and there are no treatments to those patients. So that's why I became interested in basic research because I thought by doing basic research. One day I may be able to treat, help those patients. Shina Yamanaka's design helps patients. Let's do a brilliant experiment. This took us to the limits of our knowledge. In fact, it took us beyond them and revealed something really extraordinary. There are two types of stem cells. The total total of three types of stem cells are the most important. The most important is the stem cells. These stem cells are called chryopotent. These stem cells are called chryopotent. These cells are called chryopotent because as well as making copies of them, they can become any of the different types of cells that make up the human body. So the point about the adult tissue stem cells is that these are dedicated cells to repair and maintain a particular tissue. The embryonic stem cells represent a very early stage in development. When there is no muscle or blood or bone, there's nothing else really. There's just them. Development starts with the early embryo and these pluripotent founder cells and things become more and more restricted and channeled. And that's how the body is built and it would be a complete chaos if cell type could stop turning into one another. Shina already knew from earlier experiments and cloning that development could be reversed. The despescialized cell, which scientists call differentiated, can produce embryonic cells. But no one knew how this process worked. To find out, Shina looked for clues inside the cell. I knew that ex or embryonic stem cells have factors that can combat skin cells back to embryonic state. So that's why we decided to search for such factors. Scientists had no idea what these factors were or how many would be needed. Shina went back to basics, examining the biology that gives cells their individual identities. We already knew that each cell in our body contains something that determines that what sort of tissue the cell becomes. It's cell identity. These are the genes in the nucleus. The nucleus in each of our cells contains 23% of chromosomes, made up of long strands of DNA. This is divided into sections or genes that direct the cell to make particular proteins. These proteins, which scientists sometimes call factors, are what give the cells their different identities. All of our cells contain the same genes, but in a skin cell only the genes that make skin proteins are turned on. The active genes are always in the unwound open areas of the chromosome. All the other genes that would make a liver, a heart, or an embryonic cell are turned off. They are tightly wrapped up and locked away. The remarkable thing that Shina Yamannacadid was to question whether a cell had to stay differentiated. Might it be possible to make an already specialized cell, turn back into an embryonic stem cell in the laboratory? He wondered if the same proteins that keep embryonic stem cells clura potent might be able to reprogram the specialized identity of a differentiated cell. He started with a list of over 100 possible. He didn't know if they operated alone or in combination, which would mean over a million possible variations. Using an off-the-shelf computer program, Shina Yamannacad was able to distinguish the 24 most likely candidates. It took years of work. The next step was to narrow down factors from 24 factors into whatever required. And we found that four out of the 24 factors were essential. He took a combination of four factors that normally only act together in the embryonic stem cell and inserted them into a skin cell. In a process we don't fully understand the chromosomes began to unwind. Shina's factors could now attach to the genes which make embryonic stem cell proteins. The proteins, called OCT4, SOX2, KLF4 and C-MIC, overwhelmed the competing message from the skin genes, fooling the cell into thinking it's in an embryonic environment. As these reprogrammed cells replicate, they become more and more like embryonic stem cells, until eventually they are indistinguishable. From this state, it can now be used to produce any cell in the body. What I discovered was that we can convert skin cells back to embryonic state, so we can make stem cells from skin cells. All we have to do is to add three or four factors into skin cells. That's all we need. From ESL's embryonic stem cells, we can make all the cells that exist in the body. However, we have to destroy embryos in order to generate ESL's. But, with our technology, we don't have to use embryos anymore. We can make ESL-like stem cells directly from skin cells. Shina Yamanaka had made a new type of pluripotent cell, called induced pluripotent stem cells or IPS cells. He first made his discovery studying mice, and quickly showed it also worked for human cells. This was an extraordinary discovery. Shina Yamanaka had proven he could turn a skin cell backwards in time, and then forwards into any other cell. In fact, it didn't just work with skin. He could turn any differentiated cell into an IPS cell. This generated headline news and astonished scientists all over the world. My reaction was, first of all, that this was one of the most profound scientific developments in our lifetime. It completely turned upside down everything we've been taught about development. So, we had always been taught that development was irreversible. Everything was a one-way street. But in fact, that's not true. So, our notions about development were clearly wrong. This isn't so fixed as we thought it was. It means we have to be more open in our thinking to what is biologically possible. Only Shina Yamanaka imagined that it might be possible to reprogram a differentiated cell, just a handful of proteins. Other scientists were quickly able to reproduce Shina's findings. The first step is to remove the medium we use to culture our skin cells. Now, we are adding a new medium containing the reprogramming factors. In a couple of weeks, we shall have some IPS cells in this dish. So, as a result of infecting the skin cells, what you have after a few days is this nice colonies of cells. You see here, two clear examples. So, they have an ESL morphology. But now, we also know that they have acquired these embryonic stem cells status. The way is now wide open for stem cell medicine. Injuice pluripotent stem cells, or IPS cells, are a whole new kind of cell. They can provide better ways of tightening disease and potentially regenerating the body. One of the major differences between IPS cells and embryonic stem cells is that IPS cells can be generated from individual patients. That means they are genetically identical to the individual patient. And that means if we generate, for example, cells for transplantation from IPS cells, they will not be rejected. They will not be recognized by the patient's immune system. Here, we see for the first time a perspective to derive specialized cells, for example, from the patient's skin. And to mend these cells into brain cells, into insulin producing cells, or into heart cells, which can then be used to supply this individual patient without the risk of transplant rejection. The way reprogramming works to make IPS cells is still mysterious. Although it's technically easy, it doesn't always work completely and can produce cells with unexpected changes in their genes. Scientists are now investigating how to produce perfect IPS cells that could be safe to use for treating patients. And although IPS cells provide a way of making blue-repotent cells without using human embryos, which relieves an important ethical concern, they themselves have raised entirely new issues. I wanted to avoid the usage of human embryos. So, I think we have succeeded that goal. But, as soon as we succeeded, I realized that we have generated new escalations. This was something no one had predicted. IPS cells are in theory able to create both sperm and eggs. So, they could one day be used to produce an embryo, which could be implanted and carried to town. So, one day, it may be biologically possible to create a human being from a single piece of skin. Should we stop this research? It's too late. Making IPS cells is really quite simple for anyone with basic biological training. Like all new technologies, we have to weigh up the potential benefits and potential drawbacks. For instance, studying how to make functional human sperm or eggs from IPS cells may bring benefits for infertile couples. Scientists believe that the creation of IPS cells means stem cells have entered a new era, teaching us how to control cell identity. They expect IPS cells to provide us with new tools to study disease and normal cells in the laboratory, meaning that drugs for diseases like Parkinson's can be tested on lab-grown human cells. They also hope to learn why human cells die into generative diseases like Alzheimer's. A key problem in drug development is that individual candidate drugs face the human system only at a very late stage of drug development. Until then, there's usually up to eight years of development which has gone into this individual drug. Now, using human cells at a very early stage of drug development will help to identify compounds which do not work in human cells. I think this will definitely create new opportunities to identify new drugs and speed up the process by which drugs come through, but it will just revolutionize the approach to studying inherited disease. The most important discovery in stem cell research since embryonic stem cells were first discovered in 1981. In my personal opinion, it will go down in history as one of the most amazing discoveries of all time. | ↗ |
| 244 | TED | Alan Russell: The potential of regenerative medicine | 80675 | 502 | 53 | 38.2 | positive | 21:23 | No transcript | ↗ |
| 245 | VJHemOnc – Video Journal of Hematology & HemOnc | Immunomodulation with pomalidomide in AML and high-risk MDS | 155 | | | 38.1 | | 6:11 | The premise of this study is that immune dysfunction exists in AML patients. We noted in preclinical studies that in patients who received induction chemotherapy, particularly with a time sequential chemotherapy approach whereby cytotoxic chemotherapy agents are given over serial time points in order to prime leukemia cells for apoptosis. We found that there is an increase in immunosuppressive T cell subsets, particularly regulatory T cells as well as significant T cell dysfunction at the time point when there's early recovery or early immune reconstitution after induction chemotherapy. So we hypothesized that if we can modulate these suppressive T cells at the time of early recovery after induction chemotherapy, that might lead to anti-leukemic clinical activity and perhaps synergize with cytotoxic chemotherapy. So we designed the Phase I Dose Escalation Study and ministering POMOlytomide, which is an immunomodulatory agent. It's a class of drugs called IMIDs, immunomodulatory drugs. POMOlytomide is FDA approved for multiple myeloma. POMOlytomide has actually very diverse mechanism of action, but what POMOlytomide particularly affects is a molecule known as seryblon. It targets seryblon, which is a receptor for the E3 ubiquitin ligase pathway. And by modulating seryblon, POMOlytomide leads to this selective ubiquitination degradation of two transcription factors, Iolusinicros. And Iolusinicros are important regulators of interleukin two and overall T cell immunity. POMOlytomide leads to the degradation of these transcription factors, ultimately increasing interleukin two levels. And this can have significant modulatory effects on immune subsets, as we've seen in multiple myeloma and other cancers. So we were particularly interested in giving this agent during this early lymphocyte recovery time phase after induction chemotherapy. And we designed this phase one study whereby all patients received a timed sequential chemotherapy backbone of site terabendonna rubison followed by etopocyte on days eight through ten. Again, the premise of this is that leukemia cells would be primed to apoptose after each of these cytotoxic agents are administered. And POMOlytomide was given a dose escalation at the time of early recovery with a median time point of 21 days after induction chemotherapy. This is the first study in AML with POMOlytomide. And we escalated the dose up to eight milligrams for 21 consecutive days, but notice that there are two dose limiting toxicities in this high dose level. And so we reduced the dose to four milligrams for 21 consecutive days and expanded on that cohort. And that was found to be the maximum tolerated dose. Main toxicities that we saw with the four milligram dose was rashes, which were self-limiting and able to be managed with supportive care. I think most importantly, we saw very encouraging clinical activity with the addition of POMOlytomide to patients who received induction chemotherapy in newly diagnosed AML patients. We found a 77% complete remission rate in AML patients who received the time sequential chemotherapy followed by POMOlytomide. And most importantly, we saw very encouraging clinical activity in poor risk subsets, such as those with unfavorable risk-sided genetics. We saw an 82% theory and those with AML with NDS-related changes. We saw an 85% theory. These are very poor risk subgroups that have very poor historical outcomes with conventional chemotherapy agents. The overall survival on this study was 33.8 months, which again, small numbers, but compares favorably well to historical controls. I should mention that 43 patients received POMOlytomide and the intensive chemotherapy backbone on this study. And ultimately, I think the correlates of this study were very interesting to us in that we found that POMOlytomide significantly decreased IOLOS levels as a pharmacodynamic effect. And IOLOS is a repressor of interleukin 2. And so we expected that POMOlytomide would decrease this transcription factor via its mechanism of action. And we found that mechanistically. And we also found that there were significant changes in the T-cell differentiation after administration of POMOlytomide, which ultimately led to a decrease in suppressive and senescent T-cell subsets. So we were quite encouraged by the results of this phase one study. And I think this suggests that POMOlytomide can modulate T-cell dysfunction after induction chemotherapy and may be able to abrogate the adverse risk biology of patients with unfavorable risk cytogenetics or those with AML with MDS related changes. We're looking forward to designing and developing a phase two study, adding POMOlytomide to intensive chemotherapy in patients with porous AML, newly diagnosed, untreated AML, and hope that this can be a potential future option for patients in the clinic. | ↗ |
| 246 | NASEM Health and Medicine Division | Paul Fidel - Host defense and immunomodulation of mucosal candidiasis | 286 | 2 | 1 | 38.0 | positive | 30:42 | No transcript | ↗ |
| 247 | Bedford Research Foundation | What are Induced Pluripotent Stem Cells? (iPS Cells) | 175067 | 1242 | | 37.8 | | 1:55 | No transcript | ↗ |
| 248 | CureSHANK | Webinar #1: iPSC in SHANK3 Research (Resources for Researchers Series... | 354 | 8 | 1 | 37.8 | | 1:02:57 | No transcript | ↗ |
| 249 | AR3T Regenerative Rehabilitation | The Basics of Regenerative Medicine | 1090 | 18 | 1 | 37.6 | positive | 1:01:12 | No transcript | ↗ |
| 250 | TEDx Talks | Translational research | Robert Bartlett | TEDxUofM | 14482 | 144 | 5 | 37.5 | positive | 17:10 | . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . life while we can figure out what the problem is and fix it. Now here's a diagram of the system. This machine I showed you, in fact, this is all there is to it. We put a big tube in the heart. We drain blood out. We pump it through an artificial lung, often a membrane lung, and we pump it back into the patient. And it will take over the function of the heart and lung for a significant period of time. This forum is about great, exciting new ideas. This is a great idea, but in no way is it new. This is a heart lung machine. First using the 50s for heart surgery. Then in the 60s, we know that people got working on making membrane type of lungs, which are safer and can be used for a longer period of time. And in the 70s, we treated the first newborn case, 1975, in fact, this little girl. And what do you know? She recovered and got better. Well, then we treated another one and another one. And after a while, we got to learn from our successes. We learned a lot more from the failures. And this technology started to grow in the area of newborn respiratory failure. We fought. We had to publish this work. None of the pediatric journals would publish it. Like, God, do you know there's a surgeon out there who's hooking babies to this machine? Oh, my God. Don't publish it. Other people might try and do it. But in fact, me and the technologists who were losing babies came to learn this technique from us. And we, more and more centers started up with this. And soon there were centers in academic centers around the country and in fact around the world who weren't able to do this. And they did the same things at home. Now there are about 50,000 patients who've been managed this way, not always successful. But about two thirds of them go home. Healthy and have long, healthy lives. Someone earlier was talking about saving lives. We never saved lives. We only prolong them. But if you can prolong the life of the baby for 70 years, that's worth doing. There are now about 200 ECMO centers around the world. You can see where they are. We share ideas and communicate with each other through an organization called the Extroportal Life Support Organization, or ELSO. It's based here in Ann Arb. Now you notice there are several centers in Australia and New Zealand. You might remember that swine flu epidemic that ran around the world in 2009. It started in the Southern Hemisphere. All right. All right. I can start again. I can start again. I'm just pointing out that the Australians are very good about keeping data in their health care system. So in that summer of 2009, which is our winter of 2009, they preceded our winter. It was their winter, our summer. They had 200 patients who were thought to be dying of this flu epidemic. You might remember all the press that went on. Actually, most of those patients got better with just good care. In an ICU, we had 68 of them were failing, looking like a little girl that I mentioned to you earlier. 75% of those patients walked out of the hospital. Pretty good for a fatal disease. And they published this very early so that those of us in the Northern Hemisphere learned from that planned about how many patients we might expect to have. And in fact, did pretty well with that particular epidemic. Now, medical research of the type I've been telling you about has been going on for centuries. If you're dealing with breast cancer, or cleft palate, or leprosy, or diabetes, or chronic kidney failure, or acute heart and lung failure, someone imagines that we can treat that problem better than we do now. They take that idea to the laboratory. They work on it there until they have some sort of solution, try it out in animals. If that works, take it on to patients. That's called clinical research back to the lab, back to the patients. And finally, may solve the actual problem that they started with. The NIH, about 10 years ago, invented a name for this type of research, translational research. We love that. It's the buzzword and grants these days. And it's practical, goal-oriented. Here's a problem. Let's see if we can solve it in a few years. To be differentiated from mechanistic research, I wonder why food fly genes make fruit fries, this or that, things like that. Wonderful stuff, but not going to apply clinically in a few years of time. So I'm really here to tell you about three new ideas that fall in the headline of translational research that spin off from the ECMO project. The implantable lung has completed that cycle. It's now gone to clinical practice. The artificial placenta is still in the lab phase, mulling down there. Eventually, we'll get to clinical trials. The organ bank, it's the most exciting idea, is still in the idea phase. So here's the problem. Patients who need a lung transplant with end-stage chronic lung disease, if they have an exacerbation, now they're admitted to the hospital, admitted to RICU, they come off the list. They're going to get pneumonia, they're going to get pakexia, ECMO can help a little bit, but not much, and they all die. Imagine if we had implantable artificial lung that would work for months at a time, the time it takes to get a donor for a lung, and if we had such apparatus, then patients could get up and out of bed, out of the ICU, exercise and get to be in good shape to receive a lung transplant. We've been working on this for about 15 years, in our lab, and a couple of labs in Japan and in Germany have focused on this, and we've learned the physiology and we've built artificial lungs that can be perfused by the right ventricle, and looked like they could solve this problem. The actually the first clinical trial was in Regensburg, Germany. This young lady has end-stage cystic fibrosis. She was admitted to the ICU, taken off the list, but then this device, which you see being held in the hand of the attendant, is attached to her pulmonary artery and her left atrium, had her right ventricle as pumping blood through this device. Did that for five weeks of time, a donor came up at this, when this picture's taken, she's on her way to Munich to get her lung transplant, which worked. This has now been done about 60 times around the world, so we're quite pleased with that. We've completed that cycle. What we thought might work is working quite. Well, we've done several of those patients here in an arm. Here's another problem, premature birth. The biggest problem in obstetrics and all of me in ecology, about half a million babies are born just the United States every year prematurely. If they're not too premature, the results are quite good, but the younger they are, the smaller they are, the worse the results, and 50 to 100,000 of those babies die or are permanently disabled every year. Imagine if we could maintain the fetal conditions of circulation and lung function while the lungs grew and then eventually unhook the baby from that system, we called an artificial placenta. Now, we've been at this for about five years and what we have learned is that using the ethno system, we can maintain the fetal circulation. That means no blood goes to the lungs, baby doesn't need to breathe. And in fact, we manage these fetal lambs in artificial amniotic fluid. This little oil is underwater breathing, but breathing amniotic fluid, which normal fetuses do. We can now do this for about three days when we can do it for a couple of weeks. We'll take it to the clinic. Here's another problem. Organs, which we take for transplantation in brain dead donors live for only six to 24 hours, six hours for hearts, liver, lungs, 24 hours for kidneys. After that, we can't transplant them. We have tissue culture. We can grow cells. We've been able to do that for a long time. We can put those cells in scaffolds and call it an artificial kidney, but it's really not just tissue culture. No one has ever been able to take an intact, vascularized organ and perfuse it for hours, days, weeks at a time to keep it alive. Why is that? What we think we can figure that out. Then you can imagine an unlimited supply of hearts, lungs, liver, kidneys, bone marrow, endocrine organs for elective transplantation. Not only that perfectly matched organs for transplantation, we could give gene therapy to the lung or liver and put it back in the patient gene therapy. Now it's too toxic to give to the whole patient. We could treat cancer and infection on the bench and we could do all this research on human organs, not animals. So we think about this. We can keep patients alive for a long time as I showed you. Could we keep organs alive for months of time? Well, our laboratory is applying the ECMO technology to answer that question. We're very good at perfusion. We've assembled experts in perfuseate what's stuff to use to perfuse organs. We've assembled experts who know about resuscitating damaged organs back to life. And so I hope to come back here in five years and tell you that we have solved this problem and up on the North Campus, there's a warehouse full of hard-slaunched labor's kidneys. Yes, sir. Come pick one that matches. Yes, sir. I thank you for your attention. | ↗ |
| 251 | Cardiology University of Washington | Immunomodulation and Cardiovascular Disease: Lessons learned from HIV ... | 17 | 2 | | 37.4 | | 1:01:21 | No transcript | ↗ |
| 252 | Labroots | Modeling the human brain using induced pluripotent stem cells iPSCs | 6123 | 127 | 6 | 37.3 | positive | 1:06:10 | No transcript | ↗ |
| 253 | JoVE (Journal of Visualized Experiments) | Paramyxoviruses for Tumor-targeted Immunomodulation | Protocol Preview | 108 | | | 37.2 | | 2:01 | This method can help address key challenges in the field of cancer immunotherapy by facilitating the development of oncologic vectors for targeted immunomodulation. The main advantage of the applied reverse genetic system is its versatility. Therefore, vectors can be adapted to address various research questions and target tumors with diverse immune signatures. The virus propagation steps, especially determining the optimal time point to harvest virus, are difficult to learn from a text protocol because syncytra formation must be assessed visually over time. To begin, design and clone recombinant immunomodulatory vectors as described in the manuscript. This protocol describes specific steps for the development of an oncologic measles vaccine vector, encoding a bi-specific T cell enclosure. To rescue measles virus from CDNA, 24 hours before transfection, plate measles virus producer cells evenly on a six-wall plate. Seed 200,000 cells in 2 ml DMEM containing 10% FBS per well to achieve 65 to 75% confluency at the time of transfection. Mixed 5 micrograms of recombinant DNA encoding the measles virus anti-genome that will be used to transfect the cells, appropriate plasmids, and a fluorescent reporter in a total volume of 200 microliters of DMEM. At 18.6 microliters of liposomal transfection reagent to the mixture, and immediately flick the tube to mix. Incubate this transfection mix for 25 minutes at room temperature to transfect the MB. | ↗ |
| 254 | ARDD | Jean-Marc Lemaitre at ARDD2022: Developing cell reprogramming-based st... | 856 | 31 | | 37.1 | | 22:30 | No transcript | ↗ |
| 255 | Stem Cell Therapy Experts | Stem Cell Therapy for Athletes: MLB Veteran Eduardo Pérez Shares His R... | 109 | 4 | | 36.9 | | 37:59 | No transcript | ↗ |
| 256 | Beyond the Light - Energy Harmonization Center | Unlock Your Potential: Reprogramming at a Cellular Level - Guided Medi... | 91 | 7 | | 36.8 | | 25:21 | No transcript | ↗ |
| 257 | Mayo Clinic | 3D Bioprinted Skin: Breakthroughs in Regenerative Medicine | Tomorrow'... | 2127 | 34 | | 36.4 | | 39:34 | No transcript | ↗ |
| 258 | Elliot Nicholson | Embryonic and Induced Pluripotent Stem Cells Part 1 | 9980 | 99 | 11 | 36.3 | positive | 19:34 | No transcript | ↗ |
| 259 | Simple Body Health | SENIORS: Add THIS to Your Coffee — Stem Cells Reactivate, Cancer Starv... | 11 | 2 | | 36.2 | | 28:34 | No transcript | ↗ |
| 260 | VJHemOnc – Video Journal of Hematology & HemOnc | Immunomodulation for improving long-term outcomes in myeloma | 65 | | | 35.9 | | 5:18 | When it comes to immunomodulation, I think we are all agreeing on the fact that immunomodulation is indispensable in a successful management of multiple myeloma. But of course, it's a very broad term and basically the term comes from the preclinical evidence where we see that several compounds haven't direct or indirect influence on several parts of the immune system. So in the traditional way when we talk about immunomodulation, then there are the immunomodulatory drugs with the imits, phyridomide, linalidomide, pomadeidomide. And in addition to that, the naked or traditional monoclonal antibodies that are of gimimup, I said to gimup, illogism up. But of course, we have entered now in new era. So there are the cell mods and drugs and cerebrone, e3, ubiquitin ligase modulators. And then there are the antibody drug conukates like pellomaph, the T cell engages and then last but not least the carthesis. So it's quite something. It's an area that's very rapidly evolving. And in my talk, I discussed the more traditional immunomodulation, let's say the imits and the monoclonal antibodies in newly diagnosed myeloma. And very interestingly, we see that the first line treatment become more and more stronger. And for the transplant, illegible patients, we have come quite a long way. So we are currently treating patients with triplets, combination of an imit, proteasome inhibitor and lexamethasome. And so we're now at a new era of using quadroplets. So the PI imit and lexamethasome in combination with a monoclonal antibody. And especially an anti-CV38 monoclonal antibody to get away in imit, likely in a little might and a proteasome inhibitor, e-in-id, bortesome, or carthelsome. Those quadroplets, they're really amongst the best, the most effective treatments that one can give to a newly diagnosed patients with multiple myeloma. Because these quadroplets are highly effective in terms of response, in terms of depth of response, in terms of MRD negativity. And in addition to that, they are pretty well tolerated. So these combinations can be given during many cycles. So also the duration of the induction will become longer or it will be split into two parts, say induction, then transplant, and then consolidation. For the non-transplant, irreducible patients, fortunately, there is also very favorable evolution when it comes to longer time to progression. And this is also thanks to these combinations. But one has to keep in mind that when we are talking about typical elderly myeloma patients, these are patients that are not candidates for intensive treatments. And many of these patients have comorbidities, they are frail. And somehow the treatment need to be adapted to the specific situation of those patients. But also here, a combination of an imit, likely in a little might with a proteasome inhibitor indexameter zone, so the RVD regimen is highly effective. It can be given in its standard format or in a light version for the very elderly and frail patients. And then there is the combination of linolydomite or proteasome inhibitor, like bortism with an anti-CV38, like the ratium amount, which is like the RDS of very potent combination. And that can be given for prolonged duration. So when you compare the way we approach newly diagnosed younger and elderly patients, of course there is a difference of the intensive part of transplantation. But for the rest, we see over the time more and more similarities. Again, where you have really to tailor the treatment according to the patient and according to specific characteristics of the disease. And I consider this as a very good evolution, where we are moving away from an approach like one size fits all, but that we have a basic platform and that we can modulate that platform according to the specific needs of patients. | ↗ |
| 261 | Neurological Foundation of New Zealand | Back to the future: The promise of brain cell reprogramming | Professo... | 162 | 1 | 1 | 35.7 | | 47:58 | No transcript | ↗ |
| 262 | Medical Health Institute - Wellness Experts | Part 1 of 3 - Dr. Suzanne Ferree: Clockwise Longevity with Peptides & ... | 85 | 3 | | 35.7 | | 25:55 | No transcript | ↗ |
| 263 | Bloodlesss Medicine & Surgery Society (BMSSociety) | The spectre of immunomodulation – a case for transfusion avoidance (Ne... | 311 | 12 | | 35.4 | | 18:40 | No transcript | ↗ |
| 264 | Eisenberg Family Depression Center | Induced Pluripotent Stem Cell (iPSC) Models to Study Bipolar Disorder | 2037 | 22 | 3 | 35.3 | positive | 30:35 | No transcript | ↗ |
| 265 | University of Adelaide | Stem cells: research milestones and more | 16979 | 213 | 7 | 35.0 | positive | 1:22:56 | No transcript | ↗ |
| 266 | VJOncology | ILOC: synergism of immunomodulation and tumour ablation in CRC | 46 | | | 35.0 | | 1:19 | So the eye-lock trial is a phase to non-ronomized single-arm studies where for patients having color rectal cancer with liver metastatic, we will treat them with double immunotherapy plus hyzer-regular frequency or stereotactic ablation rayotherapy. The rational behind this trial is to break the cells and liberate some new antigens that will basically be recognized by the immune system and the immunotherapy helping to increase the response rates of these patients. In fact, we will measure the efficacy of this combination treatment by measuring not the lesion that have been treated, but lesion that have not been treated to a test of the systemic effect of this combined treatment. | ↗ |
| 267 | The Health Brief | How Effective Is Immunomodulation Therapy? - The Health Brief | 23 | | | 34.8 | | 3:18 | How effective is immunomodulation therapy? How effective is immunomodulation therapy? This is a question that many people ask, especially those dealing with various health conditions. Immunomodulation therapy is all about adjusting how the immune system works. This means it can either boost or suppress immune responses based on what a patient needs. First, let's understand what immunomodulators are. These are medicines or substances that change the activity of the immune system. They are used for a wide range of diseases, including cancers, autoimmune disorders like lupus and rheumatoid arthritis, inflammatory bowel diseases, allergies, and some infections. The effectiveness of immunomodulation therapy can vary widely. For instance, in cancer treatment, immunotherapy helps the immune system recognize and attack cancer cells more effectively. This approach has shown success in treating certain types of cancer, such as melanoma and some lung cancers. In autoimmune diseases, immunomodulators work by reducing the immune system's overactivity. This helps control symptoms and slow down disease progression. Patients with rheumatoid arthritis often see significant improvements in pain and joint function when using disease modifying anti-romatic drugs or biologics. There are several types of immunomodulators. Corticosteroids are commonly used to reduce inflammation and suppress the immune system. Disease modifying anti-romatic drugs are often prescribed for rheumatoid arthritis and similar conditions. Biologics are engineered proteins that target specific parts of the immune system to control inflammation. Janus kinase inhibitors are similar and work by blocking certain enzymes involved in immune responses. While many patients experience positive outcomes, it is important to note that effectiveness is not universal. Some individuals may not respond well to immunomodulators and side effects can occur. These may include an increased risk of infections, especially with drugs that suppress the immune system or allergic reactions. The choice of therapy depends on the specific disease, the patient's overall health, and how well they tolerate the medication. In the field of regenerative medicine, immunomodulation is being studied for its potential to help the body repair tissues and reduce scarring after injuries. Early research suggests that controlling immune responses could improve healing and tissue regeneration, but this area is still being actively researched. Overall, immunomodulation therapy is a powerful tool in modern medicine. Its effectiveness depends on the specific disease, the treatment used, and the individual patient. ongoing research continues to expand its applications, especially in regenerative medicine, where controlling immune responses may help the body heal itself more effectively. | ↗ |
| 268 | Nature Portfolio | Nature Nano Talks: Nanomaterials for Immunomodulation | 8415 | 124 | | 34.4 | | 1:05:20 | No transcript | ↗ |
| 269 | Senior Health Secrets Guide | SENIORS: Add THIS to Your Coffee Every Morning — “Stem Cells Reactivat... | 5 | | | 34.2 | | 6:56 | They told you coffee was just a morning habit, a simple energy boost, maybe even something to cut back on as you get older. But what if I told you that one small addition to your daily coffee, something sitting quietly in your kitchen right now, could completely change how your body ages, not in a magical way, not in a fake overnight cure way, but in a real biological inside your cells kind of way. Because right now, inside your body, two silent battles are happening every single day. One is the slow decline of your stem cells. The very cells responsible for repairing tissues, healing damage, and keeping you feeling younger than your age. The other is the environment that allows dangerous cells, including cancer cells, to grow, survive, and spread. Most people never think about these two things. They focus on symptoms, fatigue, stiffness, brain fog, without realizing the deeper cause is happening at the cellular level. And here's the shocking part. Your morning coffee can either make both of these problems worse or help your body fight back. It all depends on what you add to it. Let me explain. As we age, stem cell activity naturally declines. This is one of the biggest reasons why healing slows down, energy drops, and the body becomes more vulnerable. You might notice cuts take longer to heal. Muscles feel weaker, or you just don't bounce back the way you used to. That's not just getting old. That's your internal repair system slowing down. At the same time, your body becomes more prone to chronic inflammation and oxidative stress. Two major conditions that create a favorable environment for disease, including cancer. Now here's where coffee becomes interesting. Coffee itself is not the enemy. In fact, high-quality coffee contains powerful antioxidants like polyphenols that help reduce oxidative stress. But most seniors unknowingly cancel out these benefits by what they add into their coffee every day. Sugar, artificial creamers, flavoured syrups, these ingredients spike insulin, increase inflammation, and feed the exact environment that harmful cells thrive in. So instead of helping your body, your morning cup quietly works against you. But when you change one thing, just one, everything shifts. There's a simple addition that has been studied for its ability to support cellular health, reduce inflammation, and create conditions that make it harder for abnormal cells to survive. That addition is turmeric. Yes, the same golden spice used in traditional medicine for centuries. The active compound in turmeric, called kerchumin, has been widely researched for its anti-inflammatory and antioxidant properties. But here's what makes it powerful when combined with coffee. Kerchumin helps reduce chronic inflammation, one of the key factors that suppress stem cell function. When inflammation is high, your body focuses on defense instead of repair. Stem cells become less active, less effective. By lowering inflammation, kerchumin may help create a more supportive environment for your body's natural repair systems. At the same time, kerchumin has been studied for its ability to interfere with pathways that abnormal cells rely on to grow. Now, let's be very clear. This is not a cure. It does not kill cancer. No food or drink should ever be seen as a replacement for medical treatment. But what it can do is support a healthier internal environment, one where your body is better equipped to protect itself. And that matters more than most people realize. Now here's how to use it the right way. Because just sprinkling turmeric into coffee won't do much if your body can't absorb it. Kerchumin on its own has low bioavailability, meaning your body struggles to use it effectively. That's why you need to combine it with a tiny pinch of black pepper. Black pepper contains piperine, which dramatically increases kerchumin absorption. Without it, most of the benefit is lost. So the simple morning routine looks like this. Freshly brewed coffee, a small pinch of turmeric, a tiny pinch of black pepper. And if you want to enhance it even further, you can add a small amount of healthy fat, like a few drops of coconut oil or a splash of unsweetened milk. Why? Because kerchumin is fat soluble, meaning it absorbs better when combined with fat. Now let's talk about what you might feel. This is not an instant energy hack like caffeine. This works gradually, quietly, at the cellular level. Over time, many people report less stiffness in the morning, better digestion, more stable energy, reduced inflammation-related discomfort, and most importantly, a feeling that their body is working with them, not against them. But there's something else you need to understand. Adding turmeric alone won't fix everything if the rest of your lifestyle is working against you. If your diet is full of processed foods, if you're constantly stressed, if you're not moving your body, then no coffee trick will save you. Think of this as one piece of a bigger system, a powerful piece, but still just one piece. Now here's a mistake many seniors make. They hear about something healthy. They try it for a few days, and then stop because they don't feel a dramatic change. But the truth is, the most important changes in your body are the ones you don't feel immediately, cellular repair, inflammation reduction, metabolic balance. These happen slowly, consistently over time, and that's exactly how real health is built. So if you're going to try this, commit to it, give it a few weeks, let your body respond. Watch how you feel over time, not just today or tomorrow, because your body is always listening to what you give it. Every morning you're either feeding inflammation or fighting it. You're either supporting repair or slowing it down, and sometimes the difference between those two paths is just one small change in your daily routine. So tomorrow morning when you reach for your coffee, pause for a second, ask yourself, is this cup helping my body or hurting it? And then make the choice that your future self will thank you for, because aging is inevitable, but how you age, that part is still in your hands. | ↗ |
| 270 | Pinnacle Integrative Health | The Healing Stack: BPC-157, TB-500, GHK-Cu, and KPV Explained | 5 | | | 34.2 | | 14:50 | Ever feel like you're doing all the right things and still wondering why your body feels off? You eat well, you train hard, your labs say you're fine, but deep down you know something's slipping. You're not alone and you're not crazy. I'm Daniel Rasmussen founder of echelon center for longevity and I've spent two decades helping high performers like you to reverse aging, re-ignite vitality and finally get answers. On unbreakable vitality we go upstream. We talk peptides, stem cells, precision diagnostic testing, reversing the age of your arteries, all the innovative science-based tools to take back your health span so that your next decades are your best yet. Because aging is real but decline is optional. Welcome back to Unbreakable Vitality where we break down the science of longevity into real-world strategies that you can actually use. Today's peptide spotlight episode focuses on one of the most versatile and powerful stacks that we use inside our regenerative protocols and our ageless future personal peptide programs. We call it the healing stack. It's a blend of BPC157, TB500, GHK copper and KPV. If you've dealt with chronic inflammation, you've got dysfunction, injuries that just won't heal, skin or connective tissue degeneration, or post viral fatigue. This combination can be transformative. Before we dive in, remember if you want to learn how we integrate peptides like those into full clinical longevity programs, come join us at the Ageless Future Longeventy Summit in Seattle. Visit AgelessFutureSeattle.com to apply. Now let's talk about why this peptide stack is one of our favorites. So when we talk about healing, we're really talking about four biological processes. First, you've got to reduce inflammation. Second, you can start restoring tissue signaling and then rebuilding structural proteins and repairing barriers like the gut lining for the skin. This healing stack addresses all four. Let's start with BPC157. Short for body protective compound. This peptide was originally isolated from the gastric juice and it's been studied for its ability to repair intestinal lining, accelerate tendon and ligament healing and restore endothelial function in blood vessels. In animal models, BPC157 has demonstrated remarkable effects at angiogenesis, which is the formation of new blood vessels, which is critical in traditional Chinese medicine. One of the main root causes for any kind of pain, dysfunction and chronic degeneration is blood stagnation, or blood stasis, leading to a lack of a oxygenation to the tissues, no nutrients, no hormones, no tissue growth factors can get in there. So angiogenesis is critical. And next, we look at TB500, which is a synthetic version of thymacin beta-4. TB500 acts like a cellular mobilizer. It promotes the migration of stem cells and repair cells into those injured areas and helps regulate actin, which is the structural protein that governs cell movement and tissue flexibility. So in practical terms, this means faster recovery for muscle strains, ligament injuries, tendonitis, surgical trauma, things like this. So when we add GHK copper in there, this is a copper binding peptide, naturally present in human plasma. GHK copper has been shown to activate over 4,000 genes associated with tissue pair, repair and regeneration. It boosts collagen synthesis, it enhances wound healing, and it improves skin elasticity. So, you know, which is why it's used both medically and cosmetically. Finally, we've got KPV, which is a tripeptide fragment, it's derived from alpha MSH. Alpha, melanocyte, stimulating hormone, MSH. So KPV is a powerful anti-inflammatory peptide that reduces cytokine activity like TNF alpha and interleukin six or IL-6. It's particularly valuable for calming inflammatory bowel conditions, autoimmune flare ups and systemic inflammation. Together, these peptides create a multi-layer healing VPC157 repairs the gut in the vascular lining, TB500, mobilizes repair cells, GHK copper, rebuilt connective tissue, and KPV quits the inflammatory storm that blocks all the healing. So in our protocols, the stack forms the backbone of many regenerative programs because it works on both structural repair and inflammatory regulation simultaneously. In terms of our ageless future protocols, this healing stack is incredibly versatile. We use it across a wide range of conditions and health goals. So for orthopedic recovery, it's one of the first stacks we deploy. Patients recovering from tendon tears, ligament injuries, joint degeneration, and often see accelerated healing when these peptides are used alongside stem cell therapies, and PRP and plasma exchange, and ozone treatments. So now also joint degeneration, right? We've got cartilage that needs to be addressed as well. Now, TB500 and VPC157, we've seen clinically as they're increasing vascularization. That's the angiogenesis and cellular migration to the injured tissue. So if you can give the body time to build and form those new micro vessels to the injured sites, now the body has improved access for healing, regeneration, and repair. So this is a game changer. Then, once that vascularization is restored, GHK copper starts to rebuild the connective tissue matrix, proteins like collagen and elastin. Another major application is gut restoration. Chronic inflammation in the gut can drive everything from brain fog to autoimmune disorders, and everything in between hits a foundational aspect of health. APC157 and KPV together help seal the intestinal lining. They seal up those tight junctions. They reduce the cytokine signaling locally, local to the gut, and they restore mucosol integrity. So we've seen clients with years of IBS symptoms start, begin for the first time to normalize their digestion in just a few weeks. And when these peptides are layered into a proper gentle detoxification protocol, phase one, two, or three detoxification, you push the toxins out, you catch them, push them in, and then they're entered into the digestive tract where we bind them, and now the bowel can eliminate them. That's the phase three detox. And also helps with rebalancing the microbiome among other protocols, nutritional supplement, probiotics, targeted based on a GIFX stool panel. But the stack is also valuable for systemic inflammation and immune dysregulation. So post viral fatigue, long COVID, and autoimmune flare ups often involve persistent inflammatory signaling. KPV dampens the cytokine cascade while GHK copper promotes tissue and repair and mitochondrial function. Then we got cosmetic and skin rejuvenation. It is another area where these the the stack really shines. GHK copper in particular has been shown in research literature to improve skin thickness, elasticity, and wound healing. So when they're combined with peptides that improve circulation and reduce inflammation, the results often extend beyond the skin and proving even hair quality and connective tissue resilience as well. Perhaps the most exciting is how this stack prepares the body for deeper rejuvenation of therapies. When inflammation is reduced, tissues begin repairing themselves. Stem cell or exosometriamins can work more effectively. In other words, this peptide stack often acts as the foundational layer before more advanced interventions. It's the preparation phase in our GPF method. So in most cases, this healing stack is delivered via subcutaneous injection on a daily basis, usually five days on, and allows peptides to enter the systemic circulation and reach those damaged tissues quickly. Now typical dose might be 250 to 500 micrograms daily for TB 500. It might be 2 to 5 milligrams weekly in GHK copper, 1 to 2 milligrams, several times a week, or we do topical applications for skin protocols. KPV, we want to get a 2 to 500 micrograms daily depending on inflammatory burden. Timing always depends on the goal. For injury recovery, we want to do peptides that are often taken consistently for four to eight weeks to accelerate that tissue remodeling. For inflammatory conditions like gut disorders, we got to go longer. Yeah, those cycles may extend eight to 12 weeks before we start tapering it. We also cycle these peptides with intention and precision and strategy. So continuous exposure to signaling molecules can eventually blunt receptors' receptiveness. So cycling allows the body to regain that sensitivity and maintain the signal effectiveness. Another key factor is stacking these peptides. The healing stack is often paired with mitochondrial peptides like MOTSC or metabolic modulators like 5-amino 1MQ. So in these cases, the healing peptides reduce inflammatory resistance while metabolic peptides enhance energy production. As always, peptide use should be guided by diagnostic testing, including baseline inflammatory markers, because the type of inflammatory markers matter. It matters which peptides we use and which what we which ones we choose. The gut panel is important. We've got to look at where your gut barrier lining dysfunction and leaky gut, what range it's in, how severe it's at, what are the inflammation markers are in the gut that like Zonielin, for example, your secretory IgA is another one that we look at, LPS. You know, all these things have to be strategically placed in an order that's going to work. Just feeling good and wanting to heal is not a diagnosis. You want to get a real diagnosis that makes the results in ribvenetal. So precision medicine always beats guesswork. The popularity of peptides has unfortunately led to a surge of online vendors selling research-only peptides. These are often advertised as a cheaper alternative to pharmaceutical grade compounds. The problem is quality control. Research peptides frequently lack sterility testing. They're not sterile. They lack accurate dosing verification and purity standards are sketchy. Independent testing has shown many of these products contain peptide sequences despite the claim that they have their own research data supporting the purity. So trust nothing that's in the gray market. It's just not worth the risk on on your health, on your genetics, on your DNA. Injecting such substances can lead to an infection, an immune reaction, or simply ineffective therapy. At Ageless Future, we use only peptide sourced from 503A and 503B compounding pharmacy. These facilities follow strict quality standards in provide pharmaceutical grade formulations. We also match peptide protocols to patient diagnostics and monitor progress through follow-up testing. This clinical oversight with safety and effectiveness. Peptides are powerful biological tools but like any advanced therapy, they should be used under proper medical guidance. Not as a biohacking, you know, experiment. If chronic inflammation and injuries or slow recovery are holding you back, the healing stack might be exactly what your body needs. At the Ageless Future longevity summit, we break down how all these peptides integrate with regenerative medicine, metabolic therapy, and personalized longevity protocols. You know, improving your health span for as long into the future as possible. That's what our definition of longevity is. Apply to attend this next summit at AgelessFutureSciattle.com and see how precision peptide therapy can help you heal faster and age stronger. Next episode, we're going to explore another fascinating peptide with huge implications for metabolic health and muscle preservation. I'll see you then. If you're feeling like your energy, your edge, or your clarity just isn't what it used to be, you're not alone. But you're also not stuck. Every week on unbreakable vitality, we explore real strategies to reverse aging, reclaim vitality, and rewrite what's possible. If today's episode gave you even one insight, pass it on. Then go take the free vascular age quiz at echelon-lonjevity.com slash quiz to see how your body's aging. Subscribe, leave a review, and follow us because your future isn't on autopilot. You are building it and you're just getting started. | ↗ |
| 271 | California Institute for Regenerative Medicine | Neural Stem Cells in the Adult Human Brain: Spotlight on Basic Researc... | 14579 | 127 | 2 | 33.9 | positive | 23:55 | No transcript | ↗ |
| 272 | All About the Immune System | What Is the Role of Immunomodulation in Infection Control? | All About... | 13 | | | 33.7 | | 2:56 | What is the role of immunomodulation in infection control? In today's health news, we are focusing on a topic that is gaining attention. The role of immunomodulation in infection control. As we face ongoing health challenges, understanding how our immune system can better respond to infections is essential. Many people are searching for ways to boost their immunity and stay healthy. So, let's break down what immunomodulation really means and how it impacts our immune response during infections. Immunomodulation plays a key role in infection control by adjusting the immune system's response to pathogens. This adjustment helps optimize defense while minimizing tissue damage. It involves regulating immune activity to maintain a balance between effective pathogen elimination and preventing excessive inflammation that can harm the body. One example of immunomodulation is the use of therapies like dupellumab. This treatment can protect against invasive infections by improving the balance of microbial communities. It works by increasing beneficial bacteria in the nasal passages, which supports immune defense. At the cellular level, immunomodulation includes stabilizing regulatory T cells. These cells releases cytokines, which are proteins that help suppress excessive inflammation during infections like sepsis. This regulation is crucial for controlling immune responses and avoiding damaging inflammation while still fighting pathogens. Moreover, certain signaling pathways in immune and nervous system cells can drive protective anti-inflammatory programs during viral infections. This reduces harmful inflammation and aids recovery. Overall, immunomodulation fine-tunes the immune system to respond appropriately to infections. It supports pathogen clearance, prevents immune overactivation, and helps maintain tissue integrity. This balance is essential for effective infection control and recovery. As research continues to evolve, the potential for new immunomodulatory therapies is promising. Scientists are working on developing treatments that can enhance the immune response without causing harm. With ongoing studies, we may see more options available for those looking to improve their immune health. In summary, understanding the role of immunomodulation in infection control can help us appreciate how our bodies fight often infections. Staying informed about these developments can empower us to make better health choices. | ↗ |
| 273 | Translational Neuropsychiatric Genomics | 14. Kristen Brennand - iPSC in schizophrenia research | 324 | 11 | | 33.6 | | 17:18 | And it's my pleasure to introduce Kristen Brinah from the Ikan School of Medicine at Mount Sinai in New York. She's a stem cell biologist and specializing in in-biter work and IPSEs as a model of skits of freeing the floors as yours Kristen. Thank you so much. Thank you. I can't share my screen until Robert stops though. Okay. So it is my my great pleasure. I think no. Yeah, no, you should be possible. There we go. Share and okay. It is my my great pleasure to get to share our work with this community today from the comfort of my own kitchen. And so what I want to talk with you guys about today is the work that we've been doing to apply stem cells to explore the genetics underlying psychiatric disease. And I'll note there's tiny little icons in each slide that there's a green camera feel free to screen grab or tweet it and if there's a red please don't. So why are we using stem cells to teach us about something as complicated and holistic as psychiatry. I think that there are two things that we're really hoping to provide to the field and and one is a new avenue by which to potentially help better diagnose patients. Genetic based diagnosis I think is something that's very obvious to this group. And we really think we have a tool to help functionally validate and link these variants that you guys are uncovering to their function in a cell type specific in donor dependent manner. And I think second and bigger picture is the real goals of course not to diagnose patients but to treat them and to do that either after the onset of symptoms or ideally prior to the onset of symptoms. And so with genetic based diagnosis we can really start thinking about drugs that one might deliver to high risk kids prior to symptom onset. And so what we're talking about here is precision medicine whereby we consider all of the risk factors and the interactions between them and any given patient and how those impact not just clinical outcomes but treatment response. And this slide is is nothing new to any of you but I want you to consider how you would feel the stem cell biologist. Somebody who really didn't know the full complexity of the genetics behind this data and and somebody who wanted to functionally validate a hit. And so this is why I'm so grateful to work with fantastic geneticists like Pell and McClar and now you like Stau and Laura Huckins because the stem cell biologist I'm not sure if you can see my cursor. I was of course drawn to that very very tall one at the top of the graph and they stopped me. They said this was a horrible locus to go after and points us instead at this one here at the gene skewering. And again they really walked me through understanding why of the entire so at the time it was the 108 but it's still true now at 145 loci. At 145 genome wide significant loci what happens at the fear and locus is the only time it happens and that's that you have the single top snip for GWAS. That's the Y-axis is also the single snot top snip for brain EQTL of a coding gene. So at fear and you have that one snip in the top right corner that is most significant for both disease and brain expression. And so that top snip here is a putative causal snip and it was one that we thought we might be able to edit by CRISPR. Now the next best examples looking more like what we see is SNAP 91 or you have 20 or 30 SNPs clustered in the top right hand corner. We don't know what's going on in that top right hand corner. We don't know if there's one put a putative causal snip in there or of each of these 30 SNPs are considering contributing three percent of the risk at the locus. So what I'll talk to you about today is the stem cell and CRISPR-based strategies by which to interrogate risk at locuses that look like or low side that look like fearing or SNAP 91. And so the the the SNAP nine or the fearing work was led by a very talented former postdoc in my lab all forever call her the bravest postdoc in my lab. I showed you on the previous slide the best data for the fearing locus but now what I'm showing you is the other side of the same data. So this is the expression in the common mind consortium brains by genotype at RS4702 the fear and snip length is schizophrenia. And what you can see is yes it is quite significant because there's 600 brains but the air bars there are daunting right and and the reason these air bars are so big is of course each of these brains came from a different individual. Each of these individuals varied at many many locations beyond just the fear and snip. I see some questions here I'll leave those till till the end. So each of these each of these donor brains varied at many genotypes genome wide. They came from donor some of whom had schizophrenia some of whom did not who had different and psychotic treatments at the time of death different drug and alcohol abuse histories. They died at different ages of different causes and had different ring values. And so our hypothesis was that if we could do this as a controlled experiment in the lab whereby nothing was different except for AA to GGG type our hope was that the effects has to be the same but the standard deviations would be much smaller. And so that is what Nadine undertook to test. Now this was a very hard edit to do we started she started this back in like 2014 I think. And the reason it was hard is we couldn't use any of the standard tricks that were developed at the time to increase the efficiency of CRISPR editing and that's because this was a single non-coding snip and editing a second single non-coding snip downstream in the PAM was just going to confound the analysis. So when she found a way and she got these edits and when she did she was able to show that in isogenic neurons from the same donor cultured in the same plate side by side when nothing more was different except AA to GGG type you could actually see a significant change in expression of the urinal levels. Moreover in the time that it took her to make these edits it was discovered that the snip in the 3-prime UTR appearance also in the binding side of a microRNA near 338. And if you inhibit near 338 in those same neurons now you can completely eliminate this EQTL effect. So it's a cell type context dependent EQTL in neurons. She was further able to show that doing nothing more than changing GGG type of a single non-coding snip was enough to manipulate neuron or right length and neuronal activity. We've been moving forward asking questions now about background. So these first edits were all done in the control background of average polygenic risk and this is now unpublished data led by a new postdoc in the lab Christina Rebick and we're asking to what extent to be snip effects vary if you do the same edits in in controls with particularly low or particularly high polygenic risk risk at syrphonia. So the same edit in both backgrounds. These are in a repository of IPS about 1200 controls from the serum collection in Kevin Egg and the Steve McAerla helped us find these extremists. And this is just our first pass. The very first pass. She's got edits now in low average and high PRS donors. This is that same activity assay and it looks like we're more sensitively resolving AA to GGG and type changes and those high PRS donors. There's a lot more work to be done here but I think it's a really exciting avenue to consider that we can now really tease out cell type and donor specific gene types effects. Now and beyond that there are so many more genes to look at than just fearing it and if you're not able to find a single period of causal to edit you need another strategy. And so here for the the next genes in the top of the list using CRISPR activation or inhibition to manipulate from the endogenous promoter the expression of these top genes and we can do it in the disease relevant direction by taking into account the EQTL direction. So here I'm just showing you by RNA seek that whether we do CRISPR A for two of these top genes, not anyone in T snare. The top gene less changing is this is a target gene, not anyone in T snare but a few you know other genes are also significantly changing and those other downstream genes that are changing seem to be enriched for brain genes, prickly, synaptic genes. We can see changes in synaptic punk die number by up and down regulating snap 91 in T snare and finally reciprocal changes in snap 91 levels up in the top panel and down in the bottom we need to reciprocal changes in a synaptic activity by electrophysiology up in the top and down in the bottom. Now of course common variants don't change in isolation. The really interesting questions what happened and they changed them together. And so here what Nadina and Sokmano did together as they did individual and combinatorial perturbations of these seem for genes in the disease relevant direction. So I'll of course not running one T snare and CLCN3 and down for fear and we have RNA seek of these individual perturbations. You can computationally predict what you think should happen when you change them all together and then you can actually do a combinatorial perturbation side by side on the same plate and ask how well the model predicted the outcomes. And so if the model is exactly right we call that no synergy but sometimes genes were too much up or too much down relative to predictions. So in fact about 82% of the time of genome wide analysis genes changed exactly as they expected the additive model predicted but 7% of the time genes were too much down and 11% of the time they were too much up. What types of genes were too much were down relative to expectations. Well they were actually synaptic genes and all the major no transmitter classes were captured here and those that were too much up while they're enriched for disorder genes particularly the rare and the common variance associated with bipolar and schizophrenia. So what we're really saying here I think is that environment context matters it's important to look at these genes in the combination of the others and here we're just looking at four common variant genes but the next experiment is moving on or 20 genes ideally 100 200 of these genes we really have to understand the interactions between these genes to get a handle on common variant effects. Now of course everything I've talked to you about now are based on the the proximal targets those genes close to this niche but the DNA is not packed into the cell in a straight line we know it's compacted and is compacted in a very deliberate and organized cell type specific fashion. And these loops can bring those schizophrenia risk variants close together to genes that are much more distant in the linear space. So this was work led by Priscilla Mergerion and collaboration with Cheryl McBarrion where he applied high c3d mapping to consider cell type specific interactions in stem cell derived neurons glia and neuroprogeny ourselves and so if there were 224 genes close to the 145 schizophrenia lowest I at the time he added a few hundred more by looking at cell type specific I see he looked at RNA importing interactions in this group and so on rich men's but he also functionally validated that these long range interactions were manipulating expression of schizophrenia risk genes. So here there was a low side where there was four schizophrenia GWAS SNPs about a hundred kilo basis away from the protein here in alpha low fias use CRISPR to delete those SNPs and was able to show that deleting these wrist SNPs changed expression of two of the three genes of the low stress in the disease relative direction. Finally with the last few minutes that I have a lot of change gears and talk about rare variants. So these are those highly penetrant where mutations in this case deletions that are very likely to result in in disorder. I'll talk to you about some work on directs in one so it's the second most significant schizophrenia where deletion the most significant for autism the only one of the ones on this slide that impacts a single gene but not to make it simple this deletion has a non-recurrent it varies between cases the boundaries and norexinal one is predicted to be spliced in hundreds of different ways. So this is a small cohort because they're rare variants collected in collaboration due to the rap report the study was led by Aaron Flayerti in collaboration with Shuzha Zhu a former postdoc in got my collaborator to go and find slab. So one of the first things Aaron was able to show is that patients from neurons had or neurons from patients had reduced neurite outgrowth. So here I'm showing you four patients the two in blue have five prime deletions where the promoter and first two exons are missing and the two in red have three prime deletions mixing missing the second third and fourth from last exons. The blue ones are in mother sun pair the red ones are mom's erotic twins and again we look at neural activity using the same as I mentioned earlier for the urine. You see reduced activity in patients drive neurons so this is a time course where you're monitoring population wide activity the controls go up with time and the patients really don't. This is a standard differentiation with a mixture of glutamaturgic and gapedrogen neurons but if you do it through a different method that yields entirely glutamaturgic neurons you see the same effect so patient cells don't fire as much. It's the question of being why they fire less because one critical rectal one isoform is missing because all the isoforms are decreased by 50% or because there's new mutant isoforms not seeing any controls. We added long range and short sequencing of the rectal one locust to ask this question we were able to identify 31 unique mutant isoforms from the three prime cases not found in the controls and then purple were indicating abundant so you can see that these mutant isoforms are some of the most abundant in the patient neurons. We found evidence that 49 or 50 50% of the wild type isoforms were significantly decreased in patient neurons and other 28 wild type isoforms were not even detected in the patient neurons but again these are somewhat at least abundant in the controls and so overall there's a mass dysregulation of the rectal one splicing repertoire. I'll add the mutant isoforms were not found in postmortem brain and most of the controls were especially the most abundant ones finally here and some functional studies to look at the impact of overexpressing these isoforms in isolation so if this is control it's neural activity on the left adding a single wild type isoform does not change activity but adding one of any four mutant erectile isoforms dramatically reduces neural activity so control neurons are impaired by a mutant isoform expression. There's five prime patients who are not predicted to have mutant isoforms have reduced activity that is rescued by overexpression of any one of four different wild type isoforms whereas the three prime patients the ones who do have mutant isoforms we can't seem to make them better whether we overexpress wild type isoforms and we can't make them worse if we overexpress mutant ones and so overall we think phenotypes are happening through two independent mechanisms both the loss of nerex and one dose and the additive effect of mutant isoform activity i think this might be more broadly applicable because if you go back into the PGC rare variant data set there are 35 nerex and one cases that have been gene-type and we think about one in five of them might be making mutant isoforms so the future studies then would be to synthesize these predicted mutant isoforms in these other cases and ask what effect they have so overall what we're really envisioning here with stem cell models is bridging the gap from gene-type to function and so i think stem cells and crisper are really good at understanding the link between DNA and RNA levels and the links between RNA levels and snap-dick function the ultimate goal of doing drug screens either the level of gene expression or snap-dick function such that we can predict patient treatment options and with that this is my final and very most important slide these are all the people who would normally be in a lab hard at work getting stem cells instead a trapped in small apartments in Manhattan and very eager to hopefully one day get back in the lab but without them there really would be no data to share with any of you today and i'm so grateful for each of them for their hard work today's talk was led by work done by Nadine Aaron Prashan and Suk in collaboration with Gabriel Gong and Shrong thank you thank you Gerstin some of this was amazing um we've got one question in the q and a for you and it's from a one-wide one um rich region of the gene fearing like x-on-inchon or promoter is the SNP RS4720 located in sorry for not making that more clear it's in the three prime utr which is why the mycoronate binding site seemed more relevant there | ↗ |
| 274 | All About the Immune System | How Does Immunomodulation Work in Treating Rheumatoid Arthritis? | All... | 12 | | | 33.5 | | 2:54 | How does immunomodulation work in treating rheumatoid arthritis? In recent days, the topic of immunomodulation in treating rheumatoid arthritis has gained significant attention. Many people are eager to learn how this approach can help manage symptoms of this challenging autoimmune condition. Rheumatoid arthritis, often abbreviated as raw, is a disease where the immune system mistakenly attacks the joints. This leads to chronic inflammation, pain, and damage to cartilage and bone. Immunomodulation focuses on adjusting the immune system's activity to reduce this inflammation and joint damage. The immune system in rheumatoid arthritis includes overactive immune cells, such as T cells, which produce inflammatory molecules. These molecules, known as cytokines, contribute to the painful symptoms of the disease. Anarchy aspect of immunomodulation is targeting these inflammatory cytokines. For example, certain medications, known as biologics, inhibit molecules like tumor necrosis factor and interleukin-6. By blocking these molecules, these treatments can help control inflammation and prevent further joint damage. Another mechanism involves modulating immune cell activation. Some therapies work by influencing receptor tyrosine kinases, which play a role in immune cell activation and cartilage degradation. By interfering with these pathways, immunomodulators can help reduce the destruction caused by immune cells. Recent studies have also highlighted the connection between gut health and the immune system. Research shows that gut microbiota can influence inflammation in the joints. This gut immune brain connection suggests that improving gut health may help in managing rheumatoid arthritis symptoms. Additionally, conventional immunosuppressive drugs are used to lower overall immune activity. These medications help reduce the immune system's attack on joint tissues, leading to better control of inflammation. Overall, immunomodulation works by adjusting the immune system, components responsible for chronic inflammation and joint damage. This approach aims to reduce symptoms, prevent disease progression, and improve the quality of life for individuals with rheumatoid arthritis. Treatments may include biologics, small molecules, or therapies targeting the interactions between the immune system and the nervous system. As research continues to advance, new treatment options are emerging, providing hope for those living with rheumatoid arthritis. | ↗ |
| 275 | Stem Cell Network - Réseau de cellules souches | What are induced pluripotent stem cells? Narrated by Dr. Mick Bhatia | 9859 | 92 | | 32.7 | | 1:06 | No transcript | ↗ |
| 276 | hPSCreg® | How to build a European iPSC Collection meeting research needs? | 14 | | | 31.9 | | 15:52 | I'm actually Julie Holder, I'm representing Rosin in South Sciences, which is actually the sort of coordinator of in collaboration with Tim's role in actually coordinating the E-Bisk consortia. And I'm going to talk about building the European IPSC collection to really meet your needs, the researchers needs, and on demand. So what my talk is going to actually be on, the overview, the introduction and the initial hot starts. And we actually really started this collection with a series of well-established IPSC lines that were available from academic collaborators and to really generate the data to allow us to make some of the decisions. Some of the information that I will be giving you is actually on this hot start and how we've actually co-really interrogated these IPSC lines and learned an awful lot from them. In addition, I'm going to talk through some very brief summaries on how we use these cells and then summarize how you can actually obtain them, which will be continued throughout this talk this morning. So it's a consortia consisting of a very large amount of partners and we all integrate together, actually working with each other to facilitate the requirements for depositing the IPSC lines and really expanding and utilizing those IPSC lines in differentiation assays to different lineages. So to build the catalog, as I said, we had these seven IPSC centers that really contributed to the hot start lines. Underline was the Sanger Hipsky lines which are of normal origin. And in addition, the FPA partners actually commissioned particular lines of interest. So we've done a lot of gene editing with Bioneer and this is something that there are a number of posters on throughout this ISSER meeting. In addition, we actually have utilized some IPSC lines from other EU funded projects. And the make-up of these lines has really fallen into some very discreet areas, mostly neurodegenerative and psychiatric cardiovascular, some minor genetic variants, metabolic such as type 2 diabetes, blood and auto-immunity and muscular skeletal disorders. The actual continuum at the bottom on that of this slide actually shows the cell line receipt from the IPSC derivation center and then the foring, we actually register it into Hipsky and we cry a number of particular vials to establish that sort of master cell bank. We then for the cell lines into various plates and culture them on in a feeder-free environment with no antibiotics and continue that throughout the expansion process. So we've had experiences of cell lines that have recovered well or haven't actually recovered well and then we QC and Glyn as Tim alluded to will actually talk a lot more on the QC data that we have established to qualify these cells moving forward. Then when the bank has actually been made of the cells, we actually transfer cells to our mirror facility at Franhoff or IBMT in Germany to actually negate the sort of issues that if one freezer goes down then we have a backup etc and we ship to E-CAC for distribution. So in the course of this project where it's anticipated that we will be establishing 280 new FPIR cell lines there will be cell line panels from diseased patients and also with normal and sibling pairs who have disease or no disease. In addition there is a number of gene edited cell lines that we are establishing and we have brought in a number of collections from Horizon 20 and IMI collaborations. So what we're building is this centralized activity in the EU for the collection testing and distribution of these well-qualified IPS lines to understandidized diverse disease representative lines and panels which are reproducible and will give you a quality of cells to actually allow you to undergo undertake your research we've concentrated because of the FPIR partners interest on most of the neurodegeneration and cardiovascular side so we have representative lines in the catalog from hunting turns from Parkinson's Alzheimer's disease etc and these will actually be expanding as the catalog is built. So it is anticipated that we could or you as a researcher could use the IPS lines to stratify the disease or stratify based on drug response using these differentiated cells in a disease environment and looking at specific disease endpoints. So the current catalog and I've had to put this qualification up that it's as of the 18th of June which is when I prepared this slide. I have had a deluge of emails to say that there's been a number of cells released so this catalog is actually changing dynamically so I would encourage you to go to the website to to ebis.com to actually look at the catalog as available and it will be demonstrated in this session but just to show the diversity of the lines that we have and that this will be building in the future. Also to note specifically in a lot of these lines there are two clones available in the catalog so you can actually build up a very comprehensive understanding of the disease etiology moving forward. So it's been a heroic effort across the whole of the consortia to actually really procure the Hipsky supplying centres to get the information from the donors, the cell history to expand cry preserve and quality control and we're really here now sort of talking about a very well established process that would result in you being able to order a particular cell from a well characterised cell bank to allow you to do the research. This gives a feel for the process steps that are involved in the expansion of the cells and routinely we would have approximately 50 within a working cell bank but the availability to go back to our master cell bank to generate passage, similar passage numbers to the initial working cell bank if required when the cells have actually the vials have been exhausted at eCAC. The QC is a this is a very general snapshot to show that we have cell phenotype genetic identity, the pluripotent potential, chromosome stability and sterility of all the the cell lines within the catalog and this actually shows a vial that is actually being distributed from eCAC with the code what passage number and it links it back to the data sheet that actually gives you all of the information on these cells. So we had these hot start lines and we had 47 in total and I just wanted to share with you how they performed during the process so remember that this is seven IPSC derivation centres. We actually had a training program so that all of the researchers supplying the cells into the bank were actually trained in all the processes that we wanted to adopt. So what media to use, how to passage them, this was actually a very well regarded workshop and as actually one of the highlights that people actually said in the whole process when it was initiated. So as you can see here there were some individual results on the recovery of the cells actually showing that there were 12.8% of the cells, there were issues recovering the cells either didn't stick down or they didn't expand, they didn't perform as expected. There was quite a high percentage of spontaneous differentiation in these cells but they were very clean with regards to viral screening but a little bit of fungal contamination across these 47 lines. However what was worrying but what does agree with literature out there was that 17% of the cells that we received in the central facility were actually not what we expected so there was some mix-ups at the actual derivation centre so a female actually was a male in one instance so you know this is something for other banking initiatives to be aware of that you do need to look at your cell line identity quite carefully. But on the positive side sorry it should be N equals 38 not 38% 38% of the cells sorry 38 of the cell lines that we received actually went on to 100% to go on to trial in each differentiation of forming mesoderm and endoderm and ectoderm. So ECAC distribution this is actually just the process showing that the files are stored in a unique ebisc freezer so there's no contamination with other cell lines of unknown microplasma levels and they're easily traceable and they're shipped within the appropriate packaging. The examples that I've got are three so this is actually a slide from one of the partners to Finnegin who actually have a hepatocyte and also pancreatic cell differentiation protocol that we have been using to actually look at the ability of the IPSC lines to differentiate into hepatocytes and pancreatic cells and this actually shows very nicely that the IPS lines that have been banked within ebisc are actually have the ability to differentiate into very well characterized hepatocytes as shown by the albumin levels and by the presence of the alpha-1 antitripsin. So this is actually a key metric to show that these cells have the ability to differentiate. This panel is actually from a bioneer line which is in the catalog showing that they differentiate to a neural lineage the map 2 are actually present on dendritic cells and total tau showing that you've actually got a good network and beta 3 beta 3 tubulin as well. So this is an example from the University of Bonn, Oliver Brussell's lab actually with a disease line and I wanted to show you the actual differentiation capabilities of a control line on the right hand side of the left hand side of the right hand panel. You've got the control line showing that you've got an increased new right length but in this hereditary spastic paraplegia or HSP you can actually see that there is a reduced new right length in the IPSCs once they've been differentiated into neurons and this is actually something that is being looked at in a drug screening campaign to see if you can recover this new right length in the disease lines. So just showing that they have the ability to to really give very good results in a differentiation capability. So just to say when summarising that we're actually building this centralized activity we're at the first stage of of really delivering the initial catalog and this is constantly changing and we will be putting in a huge amount of IPS lines from specific diseases and it's an opportunity for you to if you have an interest in generating a particular line from a rare disease then this is something please come and talk to us but we are really I think delivering to a very high standard. So just to say this is not a single entity this is a consortia and the next slide just shows the breadth of the individuals who have been involved in this and this is actually taken from the last year's general annual meeting which was held in Granta Park but we've had a more recent one in Berlin and I'm sure that if you'd like to see the slides we can actually present you with them. So thank you very much for your attention and I'll take any questions. | ↗ |
| 277 | AR3T Regenerative Rehabilitation | Regenerative Medicine 101 | 1783 | 27 | | 30.6 | | 27:29 | No transcript | ↗ |
| 278 | All About the Immune System | What Are the Main Types of Immunomodulation Therapies Available? | All... | 4 | | | 30.6 | | 2:38 | What are the main types of immunomodulation therapies available? In recent days, the conversation around immunomodulation therapies has gained traction. As people seek ways to support their immune systems, understanding these therapies is more relevant than ever. So what are the main types of immunomodulation therapies available today? Let's break it down. First up is cell-based therapy, specifically mesenchymal stem cell therapy. This approach is being studied for autoimmune conditions like multiple sclerosis. Mesenchymal stem cells can help balance the immune system by suppressing harmful T-cells and promoting protective T-cells. Clinical research has shown that this therapy can reduce disability and brain lesions in patients with multiple sclerosis. Next, we have monoclonal antibodies. These are lab engineered antibodies that target specific immune molecules. A well-known example is omelizumab, which helps reduce chronic hive symptoms by targeting immunoglobulin e-pathways. Another example is duplomab, used for chronic rhinocynositis with nasal polyps. This treatment modulates type to inflammation and can improve the microbiota in nasal passages, which may help protect against infections. Molar molecule drugs also play a role in immunomodulation. These oral medications include remibrutinib, which is effective for chronic urticaria. Other small molecules like cyclosporine can suppress the immune system but may carry risks such as kidney toxicity, so careful monitoring is essential. Conventional disease modifying anti-romatic drugs, often referred to as CD-mards, are commonly used in autoimmune diseases like rheumatoid arthritis. These drugs, including methotrexate, help reduce inflammation and immune activation. They have been standard treatments for many years and continue to be effective for numerous patients. Each type of therapy works differently, either by suppressing harmful immune activity or boosting protective immune functions, depending on the condition being treated. Ungoing research is focused on optimizing these therapies for safety and effectiveness across various immune-related disorders. As new developments emerge, staying informed can help individuals make better choices for their health. | ↗ |
| 279 | UCSF Department of Medicine | Bedside to Bench: Epithelial Cell Reprogramming in Pulmonary Fibrosis | 1381 | 25 | 2 | 30.4 | neutral | 57:51 | No transcript | ↗ |
| 280 | Dr. Regina Druz-Integrative Cardiologist | From Biomarkers to Bionerds: How Stem Cells and Exosomes Transform Hea... | 36 | 1 | | 30.4 | | 52:53 | No transcript | ↗ |
| 281 | VitaliQ Senior Health | “Chew This Tonight” – Activate 3 Stem Cell Repair Teams While You Slee... | 1 | | | 30.0 | | 13:40 | Are you waking up every morning with aching joints, dragging fatigue, and that nagging feeling your body is aging faster than it should? The shocking truth is that what you ate last night may be quietly shutting down your strongest stem cell repair program while you sleep. Hey everyone, welcome back to the channel. I'm Dr. Carter, emergency physician turned longevity researcher, and in the next 15 minutes, I'm going to hand you the simplest, most science-backed evening protocol that can literally reprogram how your body repairs itself every single night. No expensive injections, no complicated routines, just a few targeted foods and timing tweaks that most people over 35 are accidentally sabotaging right now. We're going to walk through this together, part by part, with crystal clear links, so you see exactly how each piece fits into the bigger picture. By the end you'll know precisely what to chew and when to stop chewing tonight, so your stem cells can do their best work while you rest. Let's dive in. Imagine your body as a 24-7 high-tech factory. All day long it's in production mode. You move, eat, stress, and tiny bits of damage pile up in muscles, cartilage, blood vessels, and your gut lining. But the moment you drop into deep, slow-wave sleep, everything changes. A completely different crew clocks in. Three elite populations of adult stem cells. Your hematopoetic stem cells refresh your blood and immune system. Your mizenchymal stem cells patch micro damage in muscles, joints, and connective tissue. And your intestinal stem cells, the hardest workers of all, completely rebuild the entire gut lining every three to five days. That lining isn't just for digestion. It houses about 70% of your immune cells and controls how well you absorb nutrients. Here's what most people never hear. This repair crew doesn't automatically run at full power. It depends on very specific biochemical signals triggered by what you eat and when you eat it in the final two to three hours before bed. That single window can decide whether tomorrow's version of you feels strong and resilient or stiff and drained. Imagine your body as a 24-7 high-tech factory. All day long, it's in production mode. You move, eat, stress, and tiny bits of damage pile up in muscles, cartilage, blood vessels, and your gut lining. But the moment you drop into deep, slow-wave sleep, everything changes. A completely different crew clocks in. Three elite populations of adult stem cells. Your hematopoietic stem cells refresh your blood and immune system. Your mizenchymal stem cells patch micro damage in muscles, joints, and connective tissue. And your intestinal stem cells, the hardest workers of all, completely rebuild the entire gut lining every three to five days. That lining isn't just for digestion. It houses about 70% of your immune cells and controls how well you absorb nutrients. Here's what most people never hear. This repair crew doesn't automatically run at full power. It depends on very specific biochemical signals triggered by what you eat and when you eat it in the final two to three hours before bed. That single window can decide whether tomorrow's version of you feels strong and resilient or stiff and drained. Most people think of melatonin as the sleep hormone. Inside your stem cells, it does something far more profound. It binds directly to receptors on mizenchymal stem cells and flips two critical switches. It upregulates socks too to keep stem cells versatile and stem-like. And it activates CERT-1 to delay cellular senescence. Senescent cells don't just retire. They secrete a toxic cocktail called SASP that inflames and damages neighboring healthy cells. Melatonin slows that process dramatically. The problem? After age 50, endogenous melatonin production drops 60 to 75% because the pineal gland calcifies. By your mid-60s, the nightly repair now signal is barely a whisper. In my clinical experience and after reviewing the latest circadian research, the violent drop explains why so many otherwise healthy people in their 50s and 60s suddenly feel like they've hit a wall. The fix isn't always more pills or procedures. Sometimes it's simply giving your body the raw materials at exactly the right moment. And that brings us to the single most important timing detail. Most people get completely wrong. Trip to fan is the raw material your pineal gland uses to make melatonin. Eat it at lunch and it mostly becomes serotonin, great for mood. Eat it 60 to 90 minutes before bed when darkness activates the conversion enzymes. And it becomes premium melatonin fuel, especially when paired with magnesium, zinc, and vitamin B6 as cofactors. I've tracked this myself with wearable data and seen deep sleep scores jump 20 to 30% in the first week. It's not placebo. It's precise biochemistry meeting your circadian rhythm at the perfect moment. Hematopoietic stem cells sit quietly in your bone marrow, kept dormant by steady insulin and IGF-1 signals that say, resources are plentiful, no need to activate. A heavy carb dinner or late night snack keeps those signals high all night, so renewal stays suppressed. Drop insulin with a clean 12-hour overnight fast and the message flips. Resources are limited, time to regenerate. Human studies on Ramadan fasting and Walter Longo's landmark work confirm measurable increases in circulating primitive stem cells. This isn't extreme fasting. It's simply giving your body the metabolic Q it evolved to expect every night. Your LGR-5 positive intestinal stem cells replace the entire gut lining every three to five days. Their division schedule is locked to your circadian clock genes, B-MAL-1 and clock. Irregular dinner times, late night screens, or snacking after 8 p.m. throw that clock out of sync, leading to slower renewal, leachier barriers, and those frustrating, I used to tolerate everything digestive issues. The cheapest, most effective fix, eat dinner in the exact same 30-45 minute window almost every night. It's zero cost and directly supports the stem cells guarding 70% of your immune system. Now that we understand the three core mechanisms, let's put them together into a complete, ready to use protocol, I personally follow and prescribe to patients. Here's exactly what I recommend and do most nights. 28 grams, a small handful of pumpkin seeds, 60 to 90 minutes before bed. Highest natural trip to fan source, plus magnesium and zinc, in one perfect package. 30 milliliters concentrated, montmurrency, tart cherry juice diluted in water. Delivers bioavailable melatonin, plus anthocyanins, that measurably deepen slow-wave sleep. Check with your doctor if diabetic or on statins. 30 grams Raw Walnuts, about 7 1-1-1-1-2-1-1-1-1-1-1 extra trip to fan, plus Plant Omega 3s, that keep melatonin receptors working optimally. One medium ripe banana. natural trip to fan plus highly bioavailable B6 to drive the conversion pathway. 200 to 400 milligrams magnesium glycinate 30 minutes before lights out. It's the final enzymatic key for melatonin production and reliably boosts deep sleep. Non-negotiable. Finish eating by 8 pm and fast at least 12 hours until breakfast. Water and plain herbal tea are fine, personal insight. Whole foods consistently outperform isolated supplements because the natural matrix of fiber, polyphenols and minerals changes how every nutrient is absorbed and used at the cellular level. I've tested both. The food combo wins every time on my sleep tracker and how I feel the next morning. Results build gradually. That's how real cellular repair works. Nights one through three noticeably deeper sleep and unusual morning clarity. Week one through two morning stiffness often melts away. Days 10 through 14. Steady or all day energy as gut renewal improves. Month one many see lower HSCRP inflammation markers. Month two through three faster workout recovery stronger immunity better joint comfort and visible resilience. Biggest mistakes I see and once made myself. Carb heavy dinners too late keeps insulin high and block stem cell mobilization. In consistent timing your molecular clock hates chaos alcohol within three hours of bed. Slashes deep sleep and growth hormone pulses by around 25%. Swapping everything for pills instead of whole foods. Pro tip. Parallel with a 10 minute evening wind down dim lights no screens and track sleep quality plus morning energy on a simple one through 10 scale. Patterns appear fast. After watching hundreds of patients transform with this exact approach, I've become convinced that the future of healthy aging isn't about expensive interventions. It's about stopping the small evening habits that quietly sabotage the repair systems we already have. These stem cell programs evolved over millions of years to keep us vibrant well into old age. Modern life has simply pulled us out of alignment. By giving your mizankamal stem cells the melatonin signal they crave, freeing hematopoietic stem cells from insulin suppression, and anchoring intestinal stem cells with consistent dinner timing, you're handing your body exactly what it needs to do what it was designed to do. Combine this nightly protocol with occasional 48 hour fasting resets. I'll break that down in the next video. Resistance training and smart stress management and you're creating the most complete stem cell support framework, current science supports. I've seen friends in their late 40s and 50s reverse what they thought was inevitable decline in just a few months. The science is rock solid and the results speak louder than any theory. So here's my challenge to you. Try this protocol for the next 14 nights. Track how you feel. I'm confident you'll notice the difference before the two week mark. And once you feel it you'll never want to go back. If this video hit home, drop a comment below with your biggest takeaway or write, I'm starting tonight. So I know and can cheer you on. Share it with anyone you love who's been saying they just feel older lately. And if you haven't already hit subscribe and turn on notifications so you don't miss the next deep dive into the 48 hour fasting reset that super charges all three stem cell pathways at once. Thank you for spending this time with me. Your future self, the one waking up refreshed, moving freely and staying sharp for decades to come is already smiling because of the simple choices you're about to make tonight. Sweet dreams and I'll see you in the next video. | ↗ |
| 282 | SnapTutorials | Qualia Stem Cell Review: Is It Worth Buying for Anti Aging? | | | | 30.0 | | 1:31 | In today's video, we're going to review a trending supplement called Qualia Stem Cell. First, what is Qualia Stem Cell? Qualia Stem Cell is a dietary supplement designed to support your body's natural stem cell activity. Instead of adding actual stem cells, it uses a blend of ingredients that name to help your body repair and renew itself naturally. The product contains around 15 ingredients including plant extracts, algae compounds, amino acids, and immune support nutrients. What makes it different is that you only take it for four days each month instead of daily use. Now let's talk about what it claims to do. According to the brand Qualia Stem Cell may help support tissue repair, improve recovery boost energy, and promote healthy aging. It also claims to support overall vitality including your skin muscles, brain, and immune system. Some users report feeling more energy better recovery and improved overall well-being after taking it. But others say the effects are minimal or not noticeable at all. So is it worth it? If you are someone interested in anti-aging supplements and you have the budget, you might find it interesting to try. But if you are expecting dramatic or guaranteed results, you may want to be cautious. Focus first on proven basics like proper diet sleep exercise and overall lifestyle. Qualia Stem Cell is a premium supplement with an interesting concept, but it is not a miracle product. It may offer some benefits, but the science is still limited, so manage your expectations. And that's it for this review. | ↗ |
| 283 | NIH VideoCast | Induced Pluripotent Stem Cells for Disease Modeling | 7088 | 32 | | 29.9 | | 1:06:30 | No transcript | ↗ |
| 284 | Intensive Care Society | Sepsis: Antibiotics and immunomodulation | 1193 | 17 | | 29.2 | | 59:49 | No transcript | ↗ |
| 285 | Pharmacogenomics Global Research Network | Patient-Derived Induced Pluripotent Stem Cells in Cardiovascular Preci... | 649 | 11 | | 28.7 | | 46:11 | No transcript | ↗ |
| 286 | Cure Parkinson's | How can we see if a treatment might work in humans - iPSC cell modelli... | 270 | 6 | | 28.5 | | 31:23 | No transcript | ↗ |
| 287 | HMP Education | Immunomodulation of NK cells for the treatment of lymphoid malignancie... | 8102 | 92 | 1 | 28.4 | negative | 21:05 | No transcript | ↗ |
| 288 | ASGCT | Engineered iPSC-derived Lymphocytes for Improved Cancer Therapy | 1493 | 16 | | 28.3 | | 30:47 | No transcript | ↗ |
| 289 | Yale University | Translational Medicine: From Better Ideas to Better Health | 6709 | | | 28.0 | | 57:17 | No transcript | ↗ |
| 290 | Van Andel Institute | VAI Public Lecture Series: A Focus on Translational Medicine | 295 | 6 | | 28.0 | | 1:06:39 | No transcript | ↗ |
| 291 | Seattle Science Foundation | Immunomodulation in Bone Healing: A Journey of Discovery - Charlie Cam... | 886 | 11 | | 27.7 | | 1:30:26 | No transcript | ↗ |
| 292 | CurrentProtocols | Stem Cell and Reprogramming Research Methods | 1071 | 11 | | 27.3 | | 1:00:31 | No transcript | ↗ |
| 293 | Proteintech | Best Practices for Culturing iPSCs | 879 | 9 | | 26.8 | | 53:14 | No transcript | ↗ |
| 294 | Natural Health for Seniors | Seniors: Coffee Trick Reactivates Stem Cells & Fights Cancer | Seniors... | 2 | | 2 | 26.8 | positive | 45:22 | No transcript | ↗ |
| 295 | The Qualcomm Institute | Session 1: Regenerative Medicine - Paul Frenette | 1025 | 9 | | 26.6 | | 37:52 | No transcript | ↗ |
| 296 | Thermo Fisher Scientific | Human pluripotent stem cells in understanding genetic cardiovascular d... | 711 | 8 | | 26.6 | | 1:00:59 | No transcript | ↗ |
| 297 | SRNA | Immunosuppressants and Immunomodulation for Prevention | 2504 | 4 | | 26.0 | | 31:49 | No transcript | ↗ |
| 298 | Duke Engineering | Joel Collier – Supramolecular Materials for Immunomodulation | 708 | 6 | | 25.5 | | 52:54 | No transcript | ↗ |
| 299 | Academic Medical Education | Is immunomodulation really needed to cure HBV? | Harry Janssen, MD, Ph... | 846 | 6 | | 25.4 | | 17:15 | These are my disclosures. This is an old slide where we really show what has happened. And if you look at immunotherapy over the years, the only thing which has really been licensed is peck and tephyrum. And the only antivirals that have been licensed are nucleotide analogs. So there's not a lot of diversity at all in what we have been doing over the last decades. And it's very good that we see change now. So the question is, what can be considered as cure? I don't want to go into that too deeply because Fabian already mentioned that very nicely. But I think the consensus really now is to go to functional cure. I don't know exactly what partial cures which might be important for particularly development of drugs. But most people think that HPS-Sensitum loss is what we should aim for. So the treatment paradigm is really changing from an indefinite therapy with poor off-treatment response to a fine aduration of treatment where really these nasty endpoints that we don't want to have like liver cancer and liver cirrhosis and liver related deaths are prevented. So last year, like a year ago, we had a very interesting discussion. There was a group of biologists and a group of immunologists in the room. And at the round table discussion, it went back and forth what is the role of both. And there's something to say for both would be the virological approach enough. And even within companies, there are virologists who say, well, I don't know if we need immunologists at all. Because the virologists say that blocking viral replication at multiple steps might eventually eliminate CCD and eventually curates BV infection. There will be no infected hepatocytes left. It's very debatable if that's true. It would be important though that we need better assays to really detect a very low level of replication, which we don't have in our hands now. And the other things that is mentioned is that once you decrease the viral load or the protein load, that by itself might mountain immune response, which would not need any immunological treatment. And there's some examples of that. There's modification of antiviral therapy leading to an effective immune response. For an example, stopping treatment, I'll show you in a minute. And also long-term treatment. We know that long-term treatment that people do get S-antage in loss, not at a very high extent with antivirals. But if you stop the antivirals, it's sustainable in the vast majority of the patients. And on the other side, you have the immunologies. The virus integrates. It's very difficult to get rid of CCD, NAFABN, mentioned that very clearly. And the proof is obviously that even patients who have S-antage and loss of serum version once you give them, like, profound immune suppression, they will relapse. And they will even relapse with an assasero-reversion. So that is, and we've seen that in many cases. And we do have effective immune control by giving back and deferred, although it's in a limited proportion of patients. Here's an example of what stopping therapy could do from Thomas Berg, who did the first randomized study on this, other studies are ongoing. And in the vast majority, you have a relapse of HBVDNA. But if your courage is enough not to re-initiate treatment very quickly, you have patients in there, not many, but part, let's say, 20% of your patients, where you do see an ass antigen decline, and even an ass-antage in loss. Because here you see on the left side the patients who stopped treatment and the amount of ass-antage in reduction. And on the right side, patients who continued to know of treatment, whether it was virtually no ass-antage in loss of reduction. And it was the case in patients who stopped therapy. So this is just by modifying new therapy. So theoretically, obviously, it's a very attractive option to combine the two. The agents are complementary to each other's HBV in pairs in it in adaptive immunity. And if you load a viral replication and protein load, as I mentioned, that might, by itself, enhance an immune response. And the question is whether immune therapy, and this is what many people think, currently, might tip the balance towards secure or functional cure of hepatitis B. The problem with immunotherapy is that it might have a smaller therapeutic window. You have to be very careful on how to dose these agents, because if you under-dose it, you won't have any effect. But if you over-dose it, you could get cytokine storms and all kinds of nasty side effects that we don't want to have, particularly in this hepatitis B patients, with very good treatments in our hands. Because remember, it's very different to hepatitis C, where we had a lot of back to the wall patients, and hepatitis B patients have a good therapy, and we have to give them a better therapy, but without any side effects, really. And then there's a heterogeneous response, which is very often seen. I would say more so with host targeting therapy than with virus targeting therapy. So there's a lot of different options. And there's also a treatment in the EF population, as well as a huge warehouse of patients who are already suppressed, who are on antivirals for a long time, and they might want to be cured. And if you compare the two populations, they're different. So the treatment in EF population is typically younger, have active disease. HBVDNA can be used as a biomarker. There's no resistance. And they might be more likely to accept finite treatment. And we have the suppressed population who are already on an effective and a safe treatment. They might have a partial immune restoration, which might help immune modifying therapy. They're potentially better protected against flares, but they also might have more objections to accept the experimental therapy. But particularly if they're a bit elder and they take their antivirals and they think one pill a day will keep the hepatitis away. So it's really sometimes challenging to enroll these patients into studies. Well these are all the different targets that we have. And we'll hear a lot about that this afternoon. And I'll come back to some of that in the rest of my talk. Because I thought, how can I answer this question? And I said, well, let's, if you don't know how to answer a question in science, you just try to go back to the data which are there. And as a clinician, I would like to look particularly in clinical data, because there's a lot of work done in the lab and in animal models. But that doesn't always or very often does not translate into results that we have in clinics. So I looked at the different clinical trials, which give both antivirals and immune activators both on licensed as well as on new therapies. And if you look at one of the studies which was done, it's highly cited. Most of you will have seen this before. It's combining tinoffapherin pecan-tiferin versus tinoffapherin alone and versus pecan-tiferin alone. And the authors of this paper were pretty excited that the combination did do better than the monotherapy. But if you look at the actual difference, it's very, very limited. This is I think 9% here with the combination. Nothing with tinoffapherin alone. And then the combination arms or the pecan-tiferin only arm and the short-term combination are kind of in between. And also what was interesting is that they did see S-antage and serial reversions in this particular study. And Fabian just showed the sustainability of S-loss in here. So yes, there is a bit of a better response in the combination, but it's not something that we would start massively practicing and giving our patients tinoffapherin pecan-tiferin. The benefit is just too small, really. Then another strategy where a lot of people are working on is to first decline the viral load, as I mentioned, to get rid of t-cell exhaustion. And if you do that long enough and then come in with an immune modulator where you might be more effective. So this is what we did in this particular study where we gave t-cafe here for half a year and then, and we've also done it with longer treatment and then randomized patients in either pecan-tiferin add-on or in t-cafe or alone. And the result was that indeed in the combination arm we did see a higher response rate in patients being treated with pecan-tiferin and in t-cafe versus in t-cafe or alone. But again, the difference was very, very limited, not really something to be very enthusiastic about. The interesting part of this study, in particular, those that the quality of the response was interferon, so the sustainability of response seemed to be higher with pecan-tiferin than with t-cafe. So we had more patients who off-treatment remained to in a response once they had had pecan-tiferin versus dose. We only were treated with t-cafe. So that means that that might also be very relevant for future agents that a specific response for one drug might not be as sustainable as it is for another drug, really. So that is a very difficult point also when we're discussing endpoints. So what about novel compounds? What has been done to combine antivirals and immune activators? And this is a study where capsid inhibitors, formerly owned by Novira, now by Janssen, was combined with pecan-tiferin. And again, if you look in the different categories here of patients, first on the top panel, you see HPV DNA, and then in the lower panel, you see E-antigen decline. You do see that once you combine it, you get a better response. But again, the difference with pecan-tiferin alone is not mind-boggling, really. And the problem here is that they saw a very negligible effect on E-antigen, which you might not expect with this particular compound with the capsid modulators. Then there are the patent recognition receptors, the LR agonists, RIGI, et cetera. Here is a study where we treated patients who were already on antivirals and added an immune modulator in different doses and different lengths of treatment. And the drug was very well tolerated, but the effect was limited close to zero, really. So there was definitely an effect on interferon-stimulating genes. However, it was disappointing to see that we didn't see any SD-cline in these particular patients. Some holds truth of therapeutic vaccination. We've been working on therapeutic vaccination for decades. Almost all of these studies are unfortunately negative. And every time we come in with a new vector or new peptides, and it is an interesting concept. It is, however, very challenging for people who have had this disinfection with their viral load with a huge load of proteins for decades to tip the immune balance just with the vaccine. Anyway, so what we did here is we had enough of your only group, and we had this GS4774 vaccine with the yeast-based vaccine called tarmogen packed with different epitopes. We gave different doses of the vaccine in combination with Tenoffafer and Tenoffafer alone. And it looked pretty promising here at week 24. If you looked at HBS-centrogen decline from baseline, the treatment was given for 24 weeks with a better response rate in the groups who were treated with the vaccine. However, off-treatment, so only the last 24 weeks, only Tenoffafer was given, the response was really leveled out, and unfortunately we didn't see a lot of effect of this vaccine either. Then, just as the last example, we have the checkpoint inhibitor, so PD-1, PD-L-1, inhibition can reverse immune exhaustion of HPV-specific T cells. This is done, this is work done in Germany from Rockendorf-Skope, where he really combined in an animal model, in a Wuchok model, and Tekkerfer together with the DNA vaccine, and together with an anti-PD-1 antibody. And there seemed to be an additional effect of combining these three, if you look at this blue curve, which contains all of the three components where you would have the best effect. And again, this was also done in humans in a different setting, obviously, where therapeutic vaccine was given together with nucleoside analogs and an anti-PD-1 antibody. This was done with the volumpt in the low dose, I would say, two different doses. So one group was given the volumpt alone, and in 0.1 milligram, then there are 0.3 milligrams in between. And the third group got the vaccine that I just mentioned you about, and the endpoint was 16 weeks after treatment, really. And if you look at this combination of, again, antivirals and immune modifying agents, again, there's a very modest response overall. And if you combine the group of actually nivolumap together with the vaccines, actually two immune modifying agents, it's not really better than nivolumap alone. So there is very limited evidence yet that we need immune modifiers. But then again, the antivirals are also not sufficient enough to give us the answer to functional cure. So in conclusion, ladies and gentlemen, targeting the virus, I think the therapies targeting HPV directly are effective and will come in many flavors and interfering in different steps of the replication cycle. And change in the viral load has been shown in the minority of patients to induce functional cure with S-Loss, either by long-term nucleoside analog therapy or by stopping therapy. With targeting the immune system, we're making very small steps, and we just are at the beginning of the road. So don't be in despair. I mean, we started with hepatitis C with 5% response, and we eventually got there. But the first response to antivirals, at least in the clinic, have been negative or very modest. And it's also a reason that we started very slowly, very carefully, not to induce too many side effects. Because the, again, the therapeutic window is small. There isn't a heterogeneous response, and I do think we have a long way with immune modulators to go and combination therapy is most likely needed. So to come back to my question, our immune modulators really need it to cure HPV infection. The answers I really don't know. And I do think that a lot of companies also don't know because they're infesting in both and they're combining treatments. I would say probably yes, we might need these immune modulators over time because we have no functional cure with the approach targeting the virus thus far. And I personally doubt whether we will ever will. A slight problem is that we have not find the round immune modulator really thus far, and it will be very, it will be far from easy to find this. So hopefully next year, we'll have the answer to it all. So today we're discussing this. But I really would like you invite you to come back in June 2018 at the Global Hepatitis Summit here in Toronto. You have the flyers on top of your desks, so don't throw them away like you usually do, but use them and submit an abstract, I would say, because we do have, I would say, an outstanding faculty, both from a basic science perspective as well as from a clinical perspective. Thank you very much. | ↗ |
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