ESK for "dummies"

Embryonic stem cells

Maria Shutova, Post-scienceEmbryonic stem cells and tissue stem cells are different things, and this should be well understood.

Tissue stem cells are found in a very large number of tissues of our body. They are responsible for the fact that our skin is being renewed, hematopoietic stem cells are in the bone marrow, making blood. Recently, neuronal stem cells have been discovered.

All these cells have a certain property in common with embryonic stem cells – they are all at some stage of underdevelopment. They are undifferentiated.

Embryonic cells are at the very bottom of this pyramid, and tissue stem cells are already higher, so they are called "multipotent", that is, they have the potential to turn into different cells of the body, usually within the same tissue. Therefore, they should not be confused with each other. The other properties of these cells are also quite different.

• S.L. Kiselyov, M.A. Lagarkova. Human embryonic stem cells. Nature Magazine, 2006, number 10

Embryonic stem cells are obtained from a 5-day-old human embryo. In other words, it is an embryo, in which, in fact, there are about several hundred cells. This is a blastocyst – a ball filled with embryonic stem cells. They can be isolated into culture, they grow well, they are divided almost indefinitely. They were isolated for the first time for humans more than 14 years ago and the lines that were isolated then are still cultivated by laboratories and they do not change their properties. It turns out that we are able to artificially maintain these embryonic cells in a "suspended" state, in the state in which they are in the embryo.

• Philonenko ES, Shutova MV, Chestkov IV, Lagarkova MA, Kiselev SL. Current progress and potential practical application for human pluripotent stem cells.

Unlike tissue stem cells, in addition to immortality and self–renewal, they have a wonderful property - these are the cells from which the whole body is built. That is, they can differentiate into any adult cell of the body. This property is called pluripotency. This is a very important property. There are tests for pluripotence. For example, we can make mouse cells into a mouse proper by injecting them into a mouse blastocyst. That is, you can make a mouse completely created from cells that are cultured in the laboratory. It is clear that we cannot make a human, so the only test similar to a mouse is when we inject these human embryonic stem cells subcutaneously into an immunodeficient mouse, that is, one that does not have an immune response. Often, at the site of the insertion of these cells, a teratoma is obtained – a benign tumor, it usually consists of tissues belonging to three germ leaves. This suggests that in vivo, that is, live, and not only in vitro, human embryonic stem cells can differentiate into a wide variety of tissues. Perhaps this is the reason for all the fears that they look like cancer cells, since they can endlessly divide and form teratomas in immunodeficient mice. But, in fact, cancer cells are very different. And cancer cells are some kind of broken cells that have a broken mechanism of self–maintenance and transformation into anything. In embryonic stem cells that grow in culture, nothing is broken. We keep them in the state in which they are in nature, that is, we can control them.

Thousands of scientists are engaged in controlling the fate of cells, because this field opens up great prospects when we can take embryonic stem cells and artificially make a heart, lung, liver, anything from them. Firstly, it is very interesting, because for ECC biologists it is such a Lego, they can go through the pathways of differentiation, and with their help it is possible to trace the pathways of development and the pathways of transformation of one tissue into another. Secondly, if we need to test how drugs affect embryonic cells or different pathways of development, we can do it initially in a test tube, which is also very convenient. Plus, we can introduce some mutations into these embryonic cells, such as knockouts, that is, turn off some genes that are important, for example, in embryonic development, and see what happens. If we are talking about mouse embryonic stem cells, we can even observe the phenotype, that is, how the inclusion of certain genes manifests itself at different stages of development.

Embryonic stem cells are taken from embryos that were left after the IVF procedure. Usually they are made in small quantities, some of which are planted, some are not. The part that is not hooked, with the permission of patients, parents, is given to the needs of the laboratory. And in my opinion, there is no animal husbandry in this, because these are five-day-old embryos, these are blastocysts, several hundred cells in which there is no division into either the nervous system or any kind. And as we already know from practice, these are non-specialized cells, from which anything can turn out. However, it may not work out, because no one knows whether this particular embryo will develop or not.

• International Society for Stem Cell Research (Providing a global forum for stem cell research and regenerative medicine)

Now embryonic stem cells in practice, in biomedicine, in addition to some fundamental things, are used as a universal supplier of various tissues. And, considering that we can make more differentiated derivatives and have learned to make them in quite a large amount, then we can try to do some kind of tissue replacement therapy. That is, to grow some kind of tissue that will take root in place of the damaged one. Now there are several clinical trials (conducted on embryonic stem cell derivatives), and one of the most promising tests are tests on oligodendrocytes, which are derived from embryonic stem cells. These oligodendrocytes are embryonic stem cells that are launched towards neuronal development, but this is not the final branch. They can still develop further. The idea of the test is that when a certain injury of the nervous system occurs, when neurons are restored, they cannot restore the myelin sheath around them, and without it the signals do not pass. And oligodendrocytes are the cells that create myelin sheaths. Now clinical tests are conducted on only 10-20 patients, because the main question in these tests now is whether these cells are safe or not. Today, there are still fears that when they get into a living organism, they will behave unpredictably. Successful tests have already been done on rats and monkeys. And the patients on whom these tests are done are patients of a fairly strict group who have had spinal injuries for a week before these cells are implanted in them. It is assumed that at such early stages of traumatic recovery, these oligodendrocytes help the patient to recover and restore connections in his spinal cord. It works on rats and monkeys.

Another branch of clinical trials is the production of pigment epithelial cells from embryonic stem cells. The pigment epithelium is the retina of the eye and a lot of diseases, both genetic and simply senile, are associated with it. For example, retinal dystrophy is the thinning of the retina when people gradually stop seeing. Today we are quite effectively able to make pigment epithelial cells from embryonic stem cells. Scientists are trying to plant these pigment epithelial cells in patients with retinal dystrophy. The eye is a very convenient model for monitoring graft survival.

Preliminary tests show that everything is going well, and patients are literally seeing the light. But these are preliminary studies. And so far, this practice has not gone to the clinic, but also to any more serious groups of patients. Therefore, it is too early to talk about the universal clinical use of these cells. But, nevertheless, it is already clear that this can be done. And the era of clinical use of stem cells is still very far away. All experiments with embryonic stem cell derivatives are complicated by the fact that it is still another person's cell. Immunologically, they are, as well as organs of transplantation, incompatible with the patient. This is the biggest problem of transplantation using derived embryonic stem cells.

The author is a candidate of Biological Sciences, researcher at the Laboratory of Genetic Foundations of Cellular Technologies of the Institute of General Genetics of the Russian Academy of Sciences.

Portal "Eternal youth" http://vechnayamolodost.ru27.02.2013