Channel: EuroGCT and EuroStemCell clear
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| 1 | 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. | ↗ |