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What are embryonic stem cells? What are the implications in medicine, and drug design?
So, first of all, embryonic stem cells have two defining patterns. The cell is able to make copies of itself, infinitely. The second is that it's pluripotency, that cell can turn into any cell in the body. So where do ES cells come from? Well, first the egg gets fertilized, and eventually the cells form a hollow sphere with a knot in the middle. The outside of the sphere forms the placenta. The inside of the sphere- if it gestates fully- forms the body. You can isolate the cells, and they have the properties of self-renewal and pluripotency.
What can ES cells do? Self-renewal. They have the capability to turn into any cell in the body. In the lab, however, this process is called differentiation. We know how to turn ES cells into almost every single type of cell in the body, just by changing the chemical and physical conditions. The question of the programming- going towards more specialized adult cells- back to an earlier stage- back to an ES type, this has always been a question since the 1950s when scientists learned that the genetic material in ES cells was the same as the genetic material in an adult cell. An ES cell has the same DNA as an adult cell. Different parts of that DNA are being used in different amounts. The idea was quite clear. This is possible, even though it's a bit controversial, to what extent the programming occurs naturally.
So, uh, the technologically that I am going to talk to you about is the generation of induced pluripotent stem cells, which is a technique to turn adult cells back into an embryonic state. This was in 2006 with Shinya Yamanaka in 2006. This has been reproduced and so on. How is iPS cells? Well, it started with Rudolf (something) who is now at MIT. You disrupt the virus, you take out the lethal part, and you replace it with DNA of your choice. You then infect the cell, and the virus will put its DNA or rather the construct that you engineered, and directly deposit it, stabily, in the cell. This is just going to sit there, and the cell is not going to be killed by the virus. That's an old technology.
The real science, the part that is clever, is the part where Yamanaka's group found that four genes that cause cancer, can confer properties to the engineered cell. This is, since this time, they have made vast improvements. This is a very simple and general technique. So, uh, again, the properties that they confer to these adult cells, they have self-renewal, and pluripotency. So, what is it that iPS cells can do.
In the near future of scientific discovery, there's a lot of problems in the lab. Parkinsons disease. In older patients, cells maybe spontaneously die, and the cause is not well known. The genetics are not enough to explain the disease. You can dig inside the brain to get these diseased cells, and if you did, from someone who is no longer living, we can't necessarily predict which ones will die and which ones will not. Those cells that you get from a non-living person have a limited life-span in the lab. It might take years to see the effects, like in age-dependent diseases, maybe 50 years down the road.
The iPS solution addresses some of these problems. Take the adult cells of a diseased person, and generate iPS cells from them, and turn them into neural cells. And that way, you have a much better disease model. Once you have a disease model, you can make more progress, even without the genetic basis. You can make more drugs for the targets, you can figure out if therapies are going to be toxic or not, etc.
Live iPS cells though are a long way out from being used in patients body and cells. You have a much higher risk of cancer, actually, and that's generally quite.. but yeah, that was the first one. And, so, the second issue is quality control. So, our iPS cells are completely reprogrammed, or do they share the properties? Is it safe to use them? That's a pretty massive questions. Making iPS cells takes a couple of months to do. In cases where you have a much shorter time span then this might not be practical. Getting the stem cells in the right person in the person, to get the right signals to do what you want them to do, it's always a challenge for iPS cells and ES cells.
Where stem cells do go into play is autologous versus allogenic. Autologous means from your own body, allogenic is from a donor. Your immune system can recognize self from non-self. So, basically, if you've ever heard of, trying to find a bone marrow donor, that's why it's so hard. It's to help preventing an immune system to reject the products going into your body. Patients have had organ transplants from non-family members, these people have to take immuno-suppressants for the rest of their lives. With stem cells, way in the future, you could use iPS cells in their place, to avoid the dangers. There are lots of ethical concerns with ES cells. The iPS cells lift these issues.
There are a lot of current uses of ES and iPS cells. These can change you a lot. That's about it, thank you.
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