Stem cells come out by the hour
Pyotr Smirnov, "Newspaper.Ru»
Most of the processes of our body take place in the circadian rhythm. And although modern chronobiology has been around for more than 40 years, the processes underlying this are still poorly understood. The fact that organs work "by the clock" was known in China 1.5–2 thousand years ago, but, as scientists from several medical institutes in New York have shown (Simón Méndez-Ferrer et al., Haematopoietic stem cell release is regulated by circadian oscillations - Nature advance online publication 6 February 2008), regeneration systems work in the same rhythm.
According to modern concepts, tissue repair and renewal is provided by specific progenitor cells located in tissues, or cells migrating from the bone marrow. As predicted by the St. Petersburg histologist Alexander Maksimov at the beginning of the last century, hematopoietic stem cells are able to divide and differentiate into more mature forms – "white" and "red" blood cells. This process takes place mainly within the bone marrow.
Other transformations of these cells – for example, into vascular endothelium or connective tissue fibroblasts – regularly provide regeneration and renewal processes.
Hematopoietic stem cells do not have such plasticity, that is, the ability to transform into a variety of cells of our body, as the so-called stromal cells of the bone marrow, for which this phenomenon was described thirty years ago by Novosibirsk scientists. Now it is they – multipotent mesenchymal stromal cells – that are the basis of a variety of cell therapy options. Nevertheless, hematopoietic cells are extremely important for regeneration and are widely used in medical practice.
And if mesenchymal stromal cells rarely go beyond the bones on their own, then the release of hematopoietic cells into the blood occurs regularly, and now we can even say – strictly by the hour.
New York scientists measured the content of such cells in the bloodstream of mice at different times of the standard daily cycle of 12/12, that is, 12 hours of light, 12 hours of darkness.
The maximum emission occurred at 5 hours, the minimum – at 17 hours from the beginning of the light part of the day. And five times more cells were thrown out at the maximum than at the minimum!
If at the peak of the maximum in 1 ml of blood there were 90-110 progenitor cells, then at 17 o'clock in "light time" – only 20.
Scientists went further and changed the living conditions of their wards to unusual ones. In mice that lived with the light bulb on for two weeks, the daily distribution curve rose – the minimum reached 60, and the maximum reached 120. Such changes significantly increase the ability to regenerate, but at the same time the nervous system and other regulatory systems are depleted.
The natural schedule of stem cell release was significantly changed by the sudden change of regime from night to day with a shift of 12 hours. Animals that would have been suddenly relocated from Chukotka to the Kaliningrad region would not have been able to recover as effectively as before. Rodents, who lived 2 weeks in complete darkness, threw cells into the blood in almost the same mode. And if the two-week "illumination" led to a shift of the cycle by 4 hours, then the darkness did not cause a shift.
The mechanism of such regulation, controlled by the central nervous system, did not hide from scientists either. They showed that it works as follows. Norepinephrine is released from the endings of the sympathetic nervous system, which binds to type 2 adrenergic receptors on the cells of the tissue niche. This, in turn, controls the work of the Cxcl12 gene, whose activity is in strict antiphase with the number of progenitor cells in the channel.
Unlike pure-line mice, which do not differ even in the shade of the coat, in other animals, and even more so in humans, the cycles are strictly individual.
So the discovery of American scientists must be applied in combination with the definition of the phase of the cycle. And there will be no question about the use, because today "mobilization" – an increase in the number of progenitor cells coming out of the bone marrow into the blood - is one of the main problems of cell therapy. Traditionally, the introduction of various growth factors is used for this purpose – for example, granulocyte colony stimulating factor (G-CSF), which stimulates the release of stem cells by the bone marrow. However, such "preparation" is not cheap and has a number of contraindications.
The new method requires only the selection of the correct phase of the cycle – the time of blood collection, and therefore does not even need registration and obtaining additional permits. Moreover, scientists seem to have learned how to measure time on the internal clock.
It remains to be hoped that in the near future scientists will be able to conduct large-scale studies of the role of the internal clock in the human body, and not in the mouse body.
Portal "Eternal youth" www.vechnayamolodost.ru11.02.2008