Vol 13, No 2 (2018)

This paper provides well-known as well as little-known data for initial steps of the development of transgenic mammals in the USSR, namely for the collaboration of the Department of Embryology (professor A.P. Dyban) of the Research Institute of Experimental Medicine of the Academy of Medical Sciences, USSR (Leningrad) and the Laboratory of Cellular Engineering (PhD. S.I. Gorodetsky) of the Institute of General Genetics of the Academy of Sciences, USSR (Moscow), and some details about the life journey of these research unit leaders.

The review presents literature data on embryogenesis, physiological and reparative thyroid gland (TG) regeneration in the postnatal period in terms of substantiating the presence of stem/progenitor cells in its tissue. The data concerning genetic and protein markers of thyroid stem cells, as well as markers of their thyroid differentiation, are systematized. Unresolved problems and perspectives of the use of thyroid stem/progenitor cells in tissue engineering are discussed.

Programmed necrosis or necroptosis plays an important role in cell physiology. Disturbances in necroptotic process are associated with excessive cell death, the development of a number of pathological conditions, including inflammatory and neurodegenerative diseases. Accumulated evidences suggest the involvement of necroptosis in the induction of stem cell proliferation and tissue regeneration. The necrotic death can be triggered through the family of receptors of tumor necrosis factor, TRAILR1/2, FAS, as well as endosomal Toll-like and NOD-like receptors. An important role in the regulation of necroptosis belongs to proteins RIPK1 and RIPK3, which also might be essential for proliferation of stem cells and the regeneration process. Recent study has shown that necroptosis can lead to rapid activation of progenitor cells and regeneration of the hepatic tissues, as well as a necrotic-induced tissue regeneration and differentiation of c-kit+ cells in a model of myocardial infarction. Thus, the investigation of interplay between necroptosis and regeneration of damaged tissues will allow us to understand the fundamental aspects of programmed cell death and cell division.

Neuroinflammation causes morphological and functional changes in the nervous tissue and it can be triggered by different kind of stressors. Progress of neuroinflammation as a result of post-traumatic stress disorder (PTSD) is associated with morphological changes in neurons and glial cells, as well as activation of microglia, however the exact molecular mechanisms of these changes are still unknown. In this review we discuss the connections between endocrine, immune and limbic systems during stress, the contributions of each system, the role of blood-brain barrier, as well as current methods and approaches in studying neuroinflammation.

During each period, the uterine mucosa of women of reproductive age heals without fibrosis. Previously, we established that the soluble factors that are released in this way have an antifibrotic effect on the culture of the human endometrial mesenchymal stromal cells. The objective of this work was to evaluate the antifibrotic properties of these factors on the in vitro endometrial fibrosis model. Serum menstrual and peripheral blood were obtained from a healthy donor in one day. Mesenchymal stromal cells of the endometrium were also isolated from menstrual blood. Simulation of endometrial fibrosis in vitro was carried out by differentiation of endometrial mesenchymal stromal cells into myofibroblasts under the action of TGF-ß1 (5 ng/ml). Evaluation of the effectiveness of the menstrual blood serum antifibrotic effect on the endometrial mesenchymal stromal cells and myofibroblasts derived from them was carried out by analyzing the expression of а-smooth muscle actin by immunofluorescence. Serum of peripheral blood with equal protein concentration was used as a control. Menstrual blood serum reduces the number of stress-fibrils positive for а-smooth muscle actin (a marker of myofibroblasts), both in the culture of endometrial mesenchymal stromal cells, and in in vitro modeling of endometrial fibrosis using TGF-ß1. These results indicate the presence of soluble factors in the serum of menstrual blood with antifibrotic properties. Perhaps their identification will explain the mechanisms of endometrial healing not accompanied by fibrosis. In addition, it can help to identify the causes of fibrosis of the uterine lining in gynecological diseases and develop effective methods for their treatment.

Cryopreservation of sperm is an important tool of reproductive biotechnology in the solving of the problems in infertility and reproduction of animals. In despite of the achievements in this field, the mechanisms that determine the cryoresistance of male gametes require further study. The damaging effect of ultralow temperatures during cryopreservation is primarily directed to the plasma membrane of spermatozoa. The purpose of this study is to analyze the viability of thawed bull spermatozoa after preventively induced capacitation with the further cryopreservation. Ejaculates of three noninbred bulls of Ayrshire and black-and-white breeds were used in the experiments. The functional state of spermatozoa was evaluated with a chlortetracycline test. Gametes were ranked in accordance with one of the three types of fluorescence of CTC-calcium-membrane complex : uniform fluorescence throughout the head (uncapacitated cells); fluorescence-free band in the post-acrosome region (capacitated cells); low fluorescence in the entire head, except for a thin bright fluorescence band in the equatorial segment (acrosome-reactive cells). The viability of spermatozoa was assessed with propidium iodide (5 |jg / ml). Capacitation was induced by heparin (5 jg / ml) or theophylline / dbcAMP (250/100 jM). It was shown that the induction of the capacitation of bull sperm by heparin, as well as theophylline /dbcAMP before cryopreservation enhances the number of viable sperm, reduces the number of capacitated cells and increases the number of sperm with acrosome reaction after thawing. In intact (without freezing) spermatozoa after induction of capacitation such effect is not revealed, the number of viable cells remained unchanged, the induction of capacitation caused an increase number of capacitated spermatozoa. The findings expand knowledge concerning the effects of extremely low temperatures on male gametes and can be used for modernization of the cryopreservation technology for increase their survival rate after thawing.

Multipotent mesenchymal stromal cells can be a drug for treatment of acute liver failure. The purpose of this study was to assess the effect of multipotent mesenchymal stromal cells on the proliferative, mitotic activity of hepatocytes and morphometric criteria for the regeneration of liver parenchyma after 68 % partial hepatectomy in rats. The number of mitosis, PCNA positive cells, diameter of nucleus of hepatocytes, size of hepatocytes, nuclear-cytoplasmic ratio (NCR), the area of hepatic lobules were evaluated on 1, 2, 4, 14 days after surgery. The results of the study showed that intravenous administration of allogeneic mesenchymal multipotent stromal cells from bone marrow after extended hepatectomy increase the number of proliferating hepatocytes (PCNA positive cells), but does not affect the number of mitoses, the diameter of the nucleus, the area of hepatocytes, NCR and hepatic lobules. Probably, at this time, regeneration proceeds primarily through an intracellular mechanism.