Revisiting Terminology and Characteristics of Stem Cells.

The majority of populations of differentiated cells are subject to renewal. Progenitor cells (cells-predecessors) and differentiated cells, having started the differentiation pathway or having finished it, can divide a limited number of times and are not capable of ensuring tissue regeneration during the whole period of ontogenesis. Renewal of tissues over such a long period is impossible without the participation of a specialized system which is responsible for regeneration. The given system is represented by pluripotent stem cells. Pluripotent stem cells, which conduct regeneration of all body tissues during ontogeny, are formed during implementation of the development program of the fertilized ovum, along with the formation of tissues and organs of the new organism. Being a separate direction of differentiation of embryonic cells, pluripotent stem cells are not embryonic cells. The immune system takes part in the formation of tissue-specific receptors among pluripotent stem cells. The latter remain pluripotent until the formation of tissue-specific receptors in them, and become committed (tissue-specific stem cells) after the formation of such receptors. Committed stem cells (tissue-specific stem cells) that migrate through the extracellular matrix replenish the progenitor cells of all tissues. Mesenchymal stem cells are the precursors of fibroblasts, and they only create conditions in the extracellular matrix for the migration and differentiation of committed (tissue-specific) stem cells in the places of cell death.

Immune System and Regeneration.

The review article is devoted to a role of pluripotent stem cells and immune system in renewal of tissues (regeneration). Cell-precursors (progenitor cells) and differentiated cells can be divided a limited number of times and aren't capable of ensuring regeneration of tissues during the whole process of ontogenesis. The renewal of tissues during the whole long period is impossible without the participation of a specialized system which is responsible for regeneration. The given system is made up of pluripotent stem cells which are capable of differentiating themselves into all types of somatic cells, and into a line of genital cells. These stem cells are also capable of reproducing themselves over the whole lifespan of the organism. The participation of pluripotent stem cells and the possible mediation of antigen-presenting cells and T-helpers/T-suppressors in the complex with molecules of the MHC I class/II class make it possible to consider that exactly this immune system is responsible for regeneration of tissues in the organism. The participation in the regeneration process is the most important (and perhaps the leading) function of the immune system. With age the quantity of pluripotent stem cells gradually decreases. It leads to violation of renewal of tissues at people over 35-40 years old. Transfusion of mononuclear fraction of peripheral blood procured from young donors 18-23 years old with the same blood groups and sex as the recipient (RF patent number 2350340), allows people over 40-50 years old to reestablish the pool of pluripotent stem cells and the process of tissue renewal.

Regeneration and Cicatrization.

Cicatricial tissue, being the local center of sclerosis, replaces the wound or focus of cell death. Scarring is caused by various types of injuries, including operations, as well as by a number of diseases. Scarring often culminates in the formation of strictures and other complications. Integrated stimulation of regeneration that takes the role of the immune system into account, in conjunction with the prescription of enzyme preparations possessing proteolytic activity, can be used to reduce the severity of sclerosis of damaged tissues.

Influence of Violation of Regeneration in People over 35-40 Years Old on Decrease in Production of Sexual Hormones.

With age the quantity of pluripotent stem cells gradually decreases. It leads to violation of renewal of tissues, including tissues of endocrine organs, at people over 35-40 years old. Artificial formation of the chimeral individual may be used for recovery of the pool of pluripotent stem cells in patients older than 40-50 years old. Transfusions of mononuclear fraction of peripheral blood procured from young donors 18-23 years old with the same blood groups and sex as the recipient (patent of the Russian Federation № 2350340), allows people over 40 years old to reestablish the pool of pluripotent stem cells, the process of tissue renewal and the production of sex hormones, and can also be seen as a promising way to reduce biological age, while providing a significant prolongation of life and while maintaining a high quality of life. Transfusions of mononuclear fraction of peripheral blood are required to be carried out multiple times before the restoration of the numerical strength of the recipients' pool of pluripotent stem cells is complete. The effectiveness of regeneration reconstitution in individuals older than 40 years old upon receiving transfusions of allogeneic pluripotent stem cells depends on the difference in age between the recipient and the young donor. When there is a major difference in age between young donors and recipients over 40 years old, the proliferative potential of pluripotent stem cells of donors (their ability to maintain the number of own pool) is higher than the proliferative potential of the recipient. In response to the formation of colony-stimulating growth factors, this leads to the dominance of transfused and formed colonies in the bone marrow of the donor's pluripotent stem cells over the analogous cells of recipients when renewing all of their tissues. The latter occurs mainly due to the donors' stem cells.

Regeneration and Carcinogenesis.

INTRODUCTION: Once people reach 40 years of age, they have a decrease in their pool of pluripotent stem cells, and an increased risk for development of oncological diseases. MATERIALS AND METHODS: The first part of the study was conducted in 11 patients aging 54 to 76 years old with cancer of the kidney, bladder, or prostate in stages III-IV of the disease. The second part of the study was conducted in four patients aged 60-82 years old, who were given from 4 to 7 transfusions of mononuclear fraction of peripheral blood from young donors 19-23 years old, with the same sex and blood types as the recipients, in order to restore cell regeneration. RESULTS: In the first part of the study, 1 month after chemotherapy or targeted therapy, all 11 cancer patients had leukopenia accompanied by an increase in the contents of FGFb in the blood by 1.74 times on average. Four of these patients had an increase in the level of human VEGF-A of 1.25 times on average, while three patients had an increase in the level of human EGF of 1.13 times on average. In the second part of the study, 3-6 months after the completion of a cycle of 4-7 blood transfusions of mononuclear fraction of periphery blood, four patients had an in increase in the contents of hematopoietic progenitor cells CD34+ of periphery blood by 3.25 times on average, to the level normal in young people, while the level of FGFb decreased by 1.78 times on average. Among two patients, the level of human VEGF-A decreased by 1.48 times on average, while for three patients the level of human EGF decreased by 4.12 times on average. In the buccal epithelium, all four patients had a decrease in the expression of p53 by 6.02 times on average, while three of them had a decrease in the expression of Bcl-2 by 60.0 times on average. CONCLUSION: Violation of tissue renewal is a major cause of carcinogenesis in people older than 40 years old. Excessive stimulation of mitotic activity among people over 40 can be reduced to normal levels by restoring the pool of pluripotent stem cells through transfusion of mononuclear fraction of peripheral blood from young donors 18-23 years old with the same blood groups and sex as the recipient (RF patent number 2350340).

Androgen administration in middle-aged and ageing men: effects of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume.

The gradual reduction of plasma testosterone in middle-aged and older men from mid-life onwards coincides paradoxically with the time when there is progressive growth of the prostate, a highly androgen-dependent organ. The growing interest in androgen therapy for older men makes it essential to understand the effects of exogenous testosterone on the non-diseased prostate, yet few studies are available. The present study examined prostate volume, prostate-specific antigen (PSA) and lower urinary tract symptom (IPSS) score in 207 men, aged 40-83 years, presenting with clinical features of age-related androgen deficiency [sexual and/or urinary dysfunction, elevated lutenizing hormone (LH)] who were treated for 6 months with oral testosterone undecanoate (TU). Men were divided into two groups, group 1 (n=92, plasma testosterone levels > 13 nmol/L) were treated with 80 mg daily; group 2 (n=115, plasma testosterone levels < 13 nmol/L) were treated with given 120 mg daily. Before treatment and after 1, 3 and 6 months of treatment, prostate volume was measured by ultrasound and hormones [testosterone, dihydrotestosterone, oestradiol, LH, follicle-stimulating hormone (FSH)] and PSA were measured. Within 1 month of treatment, the elevated blood LH levels were markedly decreased in all men in group 1, as well as most men in group 2. Group 2 was subdivided into men whose LH levels were suppressed (n=95, group 2a) and those whose LH levels did not suppress (n=20, group 2b). Men in group 1 and 2a had marked decreases in prostate volume, PSA and lower urinary tract symptom (IPSS) scores whereas no significant changes were observed in group 2b. Groups 1 and 2a also had more striking suppression of LH, FSH, dihydrotestosterone and oestradiol whereas group 2b had no significant increases in blood testosterone concentrations. These findings suggest that exogenous testosterone in middle-aged and older men with some clinical features of age-related androgen deficiency can retard or reverse prostate growth and that elevated plasma LH may be a useful index of severity of age-related androgen deficiency.