| 1 | 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] | ↗ |