11 March 2019

Modest successes

Medical hopes for stem cells

RIA Novosti, Tatiana Pichugina. 

Stem cells have been studied for more than half a century. Scientists create them from ordinary adult cells, simulate various diseases with their help, grow organoids for transplantation. However, therapeutic methods of using stem cells in most cases do not go beyond laboratories and clinical trials.

Cellular nursery

At the end of January, the news spread around the world: in Japan, after successful clinical trials, the treatment of spinal cord injuries with stem cells was approved. Considering that a few years ago this method was practiced exclusively on laboratory rodents, progress by medical standards is rapid. Until now, only one technology of stem cell treatment has been widely practiced – bone marrow transplantation in patients with leukemia.

All plants and animals, including humans, have stem cells. These are immature structures that can turn into any type of special cells: blood cells, neurons, skin cells, bones, muscles, teeth. With their help, the tissues of the body are constantly updated throughout life. For example, the cells of the intestinal mucosa change every week.

Stem cells were described in theory at the beginning of the XX century. For the first time, Alexander Maksimov, a biologist from St. Petersburg, suggested their existence. This was experimentally confirmed in the 1960s by Canadian scientists Ernest McCulloch and James Till.

They exposed mice to a lethal dose of X-rays, thus killing the hematopoiesis system, then transplanted them with different types of cells from healthy individuals. So the researchers saw that bone marrow cells help the blood to recover, and in order to start the renewal process, only one healthy cell is enough, but it must be immature. Now bone marrow transplantation is used to treat blood diseases all over the world.

Divine clay for the body

Any multicellular organism grows out of a small colony of stem cells. If it is divided, for example, into two parts, then a full-fledged embryo will form from each.

Embryonic stem cells can divide endlessly in vitro. This property is used to create cell cultures for laboratory experiments and testing of future drugs. Unlike stem cells in an adult body, which serve to renew a certain organ, embryonic stem cells are able to turn into any type of cell. For this, they began to be called pluripotent, that is, cells with numerous possibilities.

Technically, it is possible to obtain embryonic stem cells even of an adult. This requires a donor egg. The nucleus, where DNA is stored, is removed from it and the nucleus of another person's cell is placed there. Then the egg is forced to divide and an embryo is obtained, the development of which is stopped at the earliest stage. This was first demonstrated in 2018 by American geneticist Shukhrat Mitalipov.

So far, these achievements have no practical application, since experiments with embryonic cell cultures are allowed exclusively for research purposes.

Rejuvenation of adult cells

Stem cells in an established organism differ from embryonic ones in that they have already slightly "matured", that is, they are located in any organs and are ready to turn into the desired type of tissue. This process is irreversible. If the cell has become, for example, epidermal, then it will not be back stem.

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This was believed until 2006, when Japanese scientist Shinya Yamanaka discovered a way to genetically reprogram mature (somatic) cells into stem cells. Out of several dozen genes that trigger the development of the embryo and subsequently stop working, he identified four key ones. The scientist tried to turn them on in mature mouse cells, and it worked – they acquired the abilities of immature ones.

The proteins produced by these four genes–Oct4, Sox2, Klf4 and c-Myc– are now called the "Yamanaki cocktail". In 2012, the scientist was awarded the Nobel Prize for this achievement.

Yamanaki's discovery literally unleashed the hands of scientists around the world and generated a wave of research with these newly converted objects (they are called induced pluripotent stem cells). Biologists have mastered the idea of transplanting pluripotent stem cells into any damaged or aged organ in order to restore it. However, the reality turned out to be more complicated. The planted stem cells did not take root, died, caused side effects or simply had no effect.

The authors of the Cochrane Systematic Review (this organization investigates scientific evidence of medical manipulation) in 2015 analyzed data on the addition of stem cells to the patient's own fat cells during breast transplantation. Clinics advertising this procedure claim that the engraftment in this case goes better. However, analysts did not find any evidence of the positive effect of the procedure – on the contrary, they pointed to its possible danger.

At the same time , a systematic review of Cochrane in 2014 noted positive effect as a result of treatment of spinal injuries with mesenchymal stem cells, after which motor functions were restored faster. These experiments in those years were done exclusively on rodents and, as practice has shown, their results are applicable to the treatment of humans.

There is a huge interest in stem cells in the world, because they open the way to the treatment of many diseases: neurodegenerative, cardiovascular, diabetes mellitus, retinal damage, hereditary. Scientists are studying the possibility of growing new teeth from stem cells, restoring joints.

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