On the issue of Nobel stem cells
Unlimited possibilities
Several Nobel Prizes have been awarded for stem cell research, and our laboratory is working in all these areas.
This first happened in 2007 (the prize was awarded to Mario Capecchi, Martin Evans and Oliver Smithis "for discovering the principles of introducing specific gene modifications in mice using embryonic stem cells", ed.), although mouse embryonic stem cells were discovered in 1981. Later, in 1998, scientists managed to obtain human embryonic stem cells. It was a technological breakthrough.
Today, embryonic stem cells are only a special case of pluripotent stem cells with colossal, unlimited possibilities. Induced pluripotent stem cells (iPSCs) can be obtained using reprogramming technologies, for which the Nobel Prize in Physiology or Medicine was awarded this year. Reprogramming technology implies that it is possible to take an adult cell, introduce into it with the help of genetic manipulations four transcription factor proteins that determine the pluripotent state. After some time, the adult human cell will "rejuvenate", enter the embryonic state and acquire the properties of pluripotency.
Thus, you can take a piece of your skin, reprogram it, and then grow a completely new organism from the resulting pluripotent cells. A similar experiment was successfully conducted on mice. Cells were taken from the tail of a mouse, one of them was reprogrammed, and then a whole animal grew out of a single iPSC.
What does this give in terms of medical technologies? It is possible to take a skin or blood cell from every living person today, reprogram it to a pluripotent state, and from these pluripotent stem cells in the laboratory to obtain one or another specialized type of tissue that the patient needs.
For example, cardiomyocytes are cells of the heart muscle, or the retina of the eye.
For example, Shinya Yamanaka plans to start clinical trials for the treatment of retinal macular degeneration using pigment epithelial cells obtained from iPSCs. We are doing similar research. Some time ago, we were contacted by a family that has been suffering from a genetic disease called Stargardt's macular degeneration for several generations. With this disease, vision loss begins already in middle age. In members of this family, the mutation causing the disease has not been identified – it is not in the list of known mutations.
Their personal iPSCs were obtained from skin cells. Like Yamanaka, who, by the way, refers to us in his works, we can get the retina and pigmented epithelium of the eye from pluripotent cells. From iPSCs, we grew an eye in miniature, in the early stages of its development – it really looks like an eye. Then we began to study the expression of which genes in the patient's eye model differs from the norm, and found a mutated gene that causes degeneration of photoreceptors and pigmented epithelium. Now we need to conduct an additional experiment and make sure that it is this gene that causes the disease, although we are 99.9 percent sure of this.
In the future, we plan to correct the detected mutation in the induced pluripotent stem cells of patients – we have all the tools for this. To date, it is possible to carry out any genetic manipulation in them, including gene replacement. After that, we differentiate the corrected iPSCs into cells of the pigmented epithelium of the retina and thus get the "right" tissue – genetically restored cells for transplantation to the patient.
In October, when the prize winners were announced, a document from the Nobel Assembly of the Karolinska Institute said that induced pluripotent stem cells could be used to find new drugs. Yes.
Take, for example, such a disease as Huntington's chorea. It occurs due to an increase in the number of repeats in the huntingtin protein gene, which is why an irregular-shaped protein is produced in cells. This, in turn, leads to the death of brain neurons.
We can take skin cells from a patient with Huntington's chorea, whose genetic material contains the same number of repeats in the huntingtin gene (this gene does not work in skin cells, so they grow healthy), and get iPSCs from them. Then it is necessary to differentiate pluripotent cells into the type of neurons that suffers from this disease, and see how the physiology of the norm differs from the physiology of pathology. After that, it is possible to determine which existing chemical compounds will help normalize these physiological changes. This personalized approach is especially important for Huntington's disease, because the number of repetitions varies greatly. Here is a scheme for creating a model system for searching for medicines.
Another example is that due to cardio and hepatotoxicity, 30 percent of medicines are immediately rejected in the first phase of clinical trials. This happens because they are tested on inadequate models – on rabbit tissue samples. Now it has become possible to obtain cardiomyocytes from embryonic or induced pluripotent stem cells and test a new drug on them – on normal human cells.
Then we will be able to move to fundamentally new drug testing systems, in which the first or second phase of clinical trials will disappear or be reduced altogether, because safety checks will be carried out on a more adequate system. The time of research will be reduced and the cost of the drug will decrease. After all, about $8 billion is spent annually on these 30 percent of the funds that have gone off the course.
The most basic thing that the reprogramming technology developed by the current Nobel laureates has given is that it has allowed a fairly simple and inexpensive way to obtain personal pluripotent stem cells, for which there are already methods for growing specialized cells and tissues of the body in which genetic correction of pathology can be carried out and which allow understanding the mechanisms of the occurrence of diseases. All this allows us to call iPSCs the foundation of personalized medicine.
Portal "Eternal youth" http://vechnayamolodost.ru10.12.2012