An inexhaustible source of myelin-producing cells
How to make stem cells divide for a long time
Kirill Stasevich, Compulenta based on the materials of the University of Rochester Medical Center:
Scientists Create “Endless Supply” of Myelin-Forming Cells
One of the main problems in the treatment of stem cells is their insufficient number. Theoretically, they can replace any damaged tissue with a healthy one, but they need a lot. Meanwhile, until now, no one has been able to "persuade" these cells to divide as much as necessary. It seems that scientists from the University of Rochester Medical Center (USA) were able to solve this problem for the first time. At least in relation to the population of neural stem cells.
There are quite a lot of so-called glial cell precursors living in our brain, which give rise to different types of neuroglia cells.
Some of them, oligodendrocytes, form a myelin sheath around the neural processes, without which the neuron simply cannot work, others, astrocytes, work for neurons and the same oligodendrocytes by someone like nurses, providing them with nutrition and stable living conditions. There are high hopes associated with neuroglia stem cells: they could, for example, help restore the myelin sheath damaged due to multiple sclerosis. And, it would seem, what is easier: transplant these stem cells to the patient – and let them multiply.
However, even in laboratory conditions, it is not possible to obtain a sufficient number of these cells: they stop dividing very quickly, so that there are too few "usable" myelinating oligodendrocytes. Scientists managed to overcome this barrier by finding out the details of a complex chain of molecular interactions on which the reproduction of a stem cell depends. One of the key players here was the beta-catenin protein, which is involved in the formation of intercellular contacts. The activity of beta-catenin depends on the enzyme kinase GSK3B (glycogen synthase kinase 3 beta). The kinase puts a phosphoric acid residue on beta-catenin, after which the phosphorylated protein is sent to the scrap. However, during intensive cellular reproduction, the protein manages to avoid phosphorylation, and it is sent to the cell nucleus, where it turns on the division program.
The task of the scientists was to act on this mechanism so that the cells continued to divide as much as necessary, however, so that they did not break off the chain and did not turn into uncontrollably dividing cancer cells. This was helped by a receptor protein called PTPRZ1 phosphatase (protein tyrosine phosphatase beta/zeta). This enzyme has been known for a long time, it is present in large quantities in the precursors of glial cells, but its function remained unclear. For six years, researchers have been trying to understand its role in the cell – and finally figured it out. PTPRZ1 works in tandem with GSK3B and helps sort beta-catenins: some to the nucleus, some to cleavage. It was also possible to find the regulator of PTPRZ1 phosphatase itself: it turned out to be one of the proteins-pleiotrophins. By regulating the level of pleiotrophin, it was possible to strengthen or weaken the division of neuroglia stem cells.
That is, now science knows how it is possible to act on the signal biochemical chain from the outside without violating its integrity, without breaking its links. Although experiments were conducted only with natural precursors of human glial stem cells, the authors believe that the same mechanism will work with embryonic stem cells and induced pluripotent ones. If this is true, then doctors may have a powerful method in their hands that allows them to obtain as many stem cells as it takes to replace diseased tissue – and even more.
An article with research results (McClain et al., Pleiotrophin Suppression of Receptor Protein Tyrosine Phosphatase-beta/zeta Maintains the Self-Renewal Competence of Fetal Human Oligodendrocyte Progenitor Cells) is published in the Journal of Neuroscience.
Portal "Eternal youth" http://vechnayamolodost.ru06.11.2012