This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control. At the same time, the cell population with a higher nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic signs of the regenerative potential increase. In other experiments, Herceptin was shown to suppress only the stemness signs of MSCs, while Cisplatin seriously affected cell viability in general, reducing synthetic and proliferative activities and causing cell morphology disturbances.

The review analyzes the current state of experimental studies on the ability to obtain and cultivate stem cells from the nail organ and their possible involvement in the regeneration of a limb. It has been known that the nail unit consists of a pool of undifferentiated cells which provide sustained growth and nail repair throughout life. But, nowadays the issue of stem cell niche localization in the nail organ remains unresolved. Also, researchers demonstrated involvement of these cells in the restoration of amputated limbs, in particular, through activation of certain signaling pathways (Wnt, BMP, Notch), and epithelial-mesenchymal interactions, but the detailed mechanism of this process is poorly understood. It is supposed that the nail organ has two sources of undifferentiated cells of different origin: the proximal nail fold and the dorsal part of the nail matrix (K15+, K19+, PHLDA1+); and onychodermis (CD10+, CD34–). However, these markers are not generally accepted, so the search for markers combinations for exhaustive and complete characterization of stem cells from the nail organ continues.

Recently, numerous studies have indicated that melatonin, the hormone of pineal gland, affects the processes of differentiation of many cells, including preadipocytes into brown, beige and white adipocytes. Therefore, it is important to study the possibilities of using melatonin as a factor for the differentiation of preadipocytes to control the adipose tissue functional activity in the treatment of various diseases, including obesity. THE AIM of the study was to evaluate the morphology and functional status of brown adipose tissue at the different time of melatonin administration. MATERIALS AND METHODS. Outbred rats were divided into 3 experimental groups: control, administration of melatonin 1 hour after light-on ZT01 (Zeitgeber time), administration of melatonin 1 hour before light-off ZT11. Melatonin was administered by gavage daily for 7 weeks at a standard exposure to day-night light (12:12). RESULTS. The application of melatonin affects the morphology and functional state of brown adipocytes independently of the administration time: the nuclear-cytoplasmic ratio increases due to an increase in the area of the nucleus against the unchanging cell area. The number of lipid drops increases in each adipocyte, but their size is decreased. The effect of different time of melatonin administration was manifested in the increase of brown adipose tissue weight, in the terms of evening administrations. CONCLUSION. The effects of different times of melatonin administration at the cytological level are manifested almost identically in the brown adipocytes functional state in all experimental groups. However, at the organism level in terms of evening administrations, an increase in the relative mass of brown adipose tissue is observed, but the size of brown adipocytes do not change, which may indicate the activation of the differentiation of brown adipocytes from the progenitor cells.