Mesenchymal stem cells are the most promising regenerative medicine tool for the treatment of various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury, but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in the implementation of MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and normalization of the morphometric parameters of liver parenchyma cells. The expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both methods of transplantation, however, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.

Collagen and its derivates are typically obtained by extracting them from fresh animal tissues. Lately, however, there has been an increased interest in obtaining collagen from other sources, such as waste material, because of the growing trend to replace synthetic materials with sustainable, natural counterparts in various industries, as well as to ensure a rational waste revalorization. In this paper, collagen was obtained from non-tanned waste of leather production, taken at different stages of the production process: limed pelt, delimed pelt, and fleshings. A stepwise extraction through acid hydrolysis in 0.5 M acetic acid and subsequent precipitation with NaCl lead to collagen-containing protein extracts. The highest collagen yield was achieved in extracts based on delimed pelt (2.3% m/m after a first extraction round, and an additional 1.4% m/m after the second round). Hyp/Hyl molar ratios of 10.91 in these extracts suggest the presence of type I collagen. Moreover, gels based on these collagen extracts promote adhesion and spreading of HEK293 cells, with cells grown on collagen from delimed pelt showing a larger nuclear and cell expansion than cells grown on traditional bovine tendon atelocollagen. This suggests that these collagen gels are promising natural biomedical carriers and could be used in a wide range of medical and cosmetic applications.

Aim. To study the process of recovery of rat liver in a model of cirrhosis, which was induced by intraperitoneal injection of CCl4, after transplantation human umbilical cord MSCs. Today in the world as an alternative to liver transplantation is offered cell therapy, which leads to the recovery of organ’s functions through the injection of MSCs. The key role of MSCs in the development of fibrosis and its final stage - liver cirrhosis is the inhibitory effect on the proliferation of the extracellular matrix. Methods. The methods of histology and morphometry were used in the work. Results. It was found, that 13 weeks after CCl4 induction, the amount of collagen increased 7 times, atrophic, sclerotic changes in the architectonics of rat liver and functional disorders of hepatocytes were observed. After transplantation of human umbilical cord MSCs - 6-7x106 cells / kg body weight of the animal, was shown that after 3 weeks the rate of collagen accumulation decreased and after 13 weeks the amount of ECMs and other morphometric indexes almost corresponded to the negative control. Conclusions. Studies have shown that transplantation MSCs from human umbilical cord leads to almost complete regeneration of the rat liver which was caused by experimental liver cirrhosis with intraperitoneal injection of CCl4. Keywords: human umbilical cord MSCs, extracellular matrix, hepatocytes.

Mesenchymal stem cells (MSCs) have unique properties that ensure the regeneration of damaged tissues, which allows using them in the cell therapy of various diseases. The realization of these properties is mainly related to the interaction of MSCs with macrophages. Aim. To study the interaction of the human umbilical cord MSCs with macrophages in vivo using a model of sterile inflammation of the peritoneal cavity in mice. Methods. Cytological methods for assessing acute inflammation of the peritoneal cavity of mice, isolation and cultivation of the human umbilical cord MSCs, study of the expression of the MSC surface markers by flow cytometry, determination of the phagocytic activity of mononuclear cells of peritoneal cavity, isolation of mononuclear RNA, RT-PCR, methods of statistical analysis. Results. The dynamics of the development of the MSCs' therapeutic effect after their transplantation into the peritoneal cavity of mice was studied; a method for assessing the therapeutic activity of various MSC preparations was developed; the fast polarization of macrophages to the M2 state after the injection of MSCs was shown, by studying the phagocytic activity of macrophages and expression of the IL-10 gene. Conclusions. The most effective method to increase the therapeutic potential of MSCs is preconditioning with low doses of H 2 O 2 . K e y w o r d s: MSCs, macrophages, peritonitis.