How to rejuvenate stem cells

Kirill Stasevich, "Science and Life"The cells of our body age and fail over time.

The fact that our organs do not stop working at the same time is the merit of stem cells, the stock of which we keep throughout life. Recently, stem cells have been actively studied, and their popularity is only growing, since it is assumed that they will open the way for us to regenerative medicine.

Unlike an ordinary, specialized cell – a neuron, a hepatocyte, an epithelial cell, etc. – a stem cell can do nothing but divide. Her offspring either retains the parental stem properties, or takes a step towards specialization. In general, stem cells have many varieties, among them the most immortal and the most non-specialized, if I may say so, are embryonic stem cells, which can divide almost indefinitely and which can give rise to any of the more than 200 varieties of cells in our body. There are also more specialized stem cells that serve a specific tissue or organ. For example, hematopoietic cells give rise to blood cells, from immune cells to erythrocytes, but a neuron from a stem cell of this kind will not work. However, even such partially specialized stem cells retain the ability to potentially infinite division. Finally, the progenitor cells, or progenitor cells, are the closest to ordinary, specialized cells. Their number of divisions is already limited, they have already irreversibly embarked on the path of differentiation.

Although, according to some data, even in an adult organism, some small proportion of absolutely "omnipotent" cells resembling embryonic cells remains, yet the vast majority of "adult" stem cells already have specialization to one degree or another. Each tissue, each organ has its own population of stem and progenitor cells, which can, if anything, update the aging cellular composition. (Recall that even in the brain it was possible to find areas where new neurons are being formed, although this process is not so intense as to renew the entire brain.)

Stem cells have been used for a long time – and not unsuccessfully – for medical purposes. And it's not just about replacing the burned areas of the skin with new ones grown in a test tube in case of severe burns. With the help of stem technologies, you can create elements of the retina of the eye and transplant it to the blind, or grow insulin-producing pancreatic cells and transplant them to diabetics, or grow new neurons and transplant them to those who have had a massive stroke. In general, huge practical prospects open up for stem cells.

But pretty quickly, the researchers encountered several specific problems related to cellular "raw materials". If we take "omnipotent" embryonic stem cells, then ethical difficulties arise here – is it possible to disassemble a human embryo for spare parts? Relatively recently, embryonic material has been replaced by learning to convert ordinary cells of the body into an undifferentiated, stem state. That is, now it has become possible to obtain, for example, neurons from epithelial skin cells – through an intermediate stem state. At the same time, immunological difficulties are eliminated, because the "final product" is transplanted to the same person from whom the "raw materials" were taken. 

But such a procedure is fraught with the unpredictability of artificial stem cells, which can, for example, be reborn into a malignant tumor (although the optimization of the method continues, and there is hope that such cells will soon become completely obedient). Could it not be simpler to make our own semi-specialized stem cells of the human body work, which, as we remember, remain with us for life?

Here a new problem arises related to aging. Although stem and progenitor cells retain the ability to divide, the overall age of the body affects them too. The scientific project of Anastasia Efimenko from Moscow State University, called "The influence of risk factors on stem and progenitor cells and the processes of repair and regeneration in the body", is just devoted to how aging and disease affect the properties of stem cells. The researchers were able to show that cardiovascular and metabolic diseases, such as coronary heart disease and diabetes mellitus, coupled with age weaken the ability of stem cells to divide and synthesize bioactive molecules necessary for regenerative processes. Which is understandable – after all, diseases hit all the cells of the organ, including those that should restore this very organ.

That is, if we are talking about cell therapy methods for an elderly patient, then we must imagine exactly what his stem cells can and cannot do. And we need to know what a person was sick with, what lifestyle he led, and what risk factors his stem and progenitor cells were exposed to. In other words, a personalized approach is needed, which is being talked about more and more often in modern medicine. So it would not be an exaggeration to say that the stem cell project, which recently received the Moscow Government Prize for young scientists, is at the forefront of modern biotechnological science.

But if we managed to find out that stem cells do not feel very well due to age, can we somehow rejuvenate them? Such possibilities are being actively explored. As an example, we can cite last year's work by Stanford University staff published in Nature Medicine, in which the authors, using the example of mice, described a way to rejuvenate muscle stem cells through one of the cellular signaling pathways (Cosgrove et al., Rejuvenation of the muscle stem cell population restores strength to injured aged muscles – VM). In such cases, it is important to know what exactly should be repaired, which molecular processes require intervention. The experiments of A. Efimenko and her colleagues showed that age and disease strongly affect the VEGF protein, or vascular endothelial growth factor – stem cells stop synthesizing it and therefore their stem properties deteriorate considerably.

If the cells are injected with an additional VEGF gene, they will rejuvenate; this is manifested, among other things, in the fact that modified stem cells and progenitor cells more actively stimulate vascular growth and restore blood flow in ischemic tissues. Researchers are also developing other genetic tools for cell repair, and those that already exist have successfully passed most stages of preclinical trials. However, unfortunately, it does not go further – clinical research stumbles upon the lack of proper laws that would regulate cellular experiments in the clinic, no matter how promising in the sense of public benefit they may be.

Portal "Eternal youth" http://vechnayamolodost.ru06.03.2015