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We studied the effect of mesenchymal stromal cells and conditioned media on healing of full-thickness skin wound in rats. Cell transplantation to the wound bed did not accelerate wound closing and had no effect on the severity of inflammation, but increased vasculariza - tion of the granulation tissue in 14 days after injury. After injection of conditioned medium to the wound, less pronounced inflammation or enhanced epithelialization was observed. The angiogenic effect was observed only after repeated administration of conditioned medium and was associated with slower regeneration, probably due to skin traumatization by repeated injections. At the same time, fetal skin fibroblasts stimulated angiogenesis only after transplantation in high doses and the medium conditioned by these fibroblasts had no effect on wound healing.

Hepatitis C virus (HCV) is one of the major causes of chronic liver disease and leads to cirrhosis and hepatocarcinoma. Despite extensive research, there is still no vaccine against HCV. In order to induce an immune response in DBA/2J mice against HCV, we obtained modified mouse mesenchymal stem cells (mMSCs) simultaneously expressing five nonstructural HCV proteins (NS3-NS5B). The innate immune response to mMSCs was higher than to DNA immunization, with plasmid encoding the same proteins, and to naïve unmodified MSCs. mMSCs triggered strong phagocytic activity, enhanced lymphocyte proliferation, and production of type I and II interferons. The adaptive immune response to mMSCs was also more pronounced than in the case of DNA immunization, as exemplified by a fourfold stronger stimulation of lymphocyte proliferation in response to HCV, a 2.6-fold higher rate of biosynthesis, and a 30-fold higher rate of secretion of IFN-γ, as well as by a 40-fold stronger production of IgG2a antibodies to viral proteins. The immunostimulatory effect of mMSCs was associated with pronounced IL-6 secretion and reduction in the population of myeloid derived suppressor cells (MDSCs). Thus, this is the first example that suggests the feasibility of using mMSCs for the development of an effective anti-HCV vaccine.

Hematopoiesis is the main function of the liver during a considerable period of mammalian prenatal development. Hematopoietic cells of the fetal liver exist in a specific microenvironment that controls their proliferation and differentiation. This microenvironment is created by different cell populations, including epitheliocytes, macrophages, various stromal elements (hepatic stellate cells, fibroblasts, myofibroblasts, vascular smooth muscle and endothelial cells, mesenchymal stromal cells), and also cells undergoing epithelial-to-mesenchymal transition. This paper considers the involvement of these cell types in the regulation of fetal liver hematopoiesis.

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