FEATURES OF THE CELL CYCLE OF HEPATOCYTES IN EXPERIMENTAL AUTOIMMUNE HEPATITIS ON THE BACKGROUND OF THE USE OF PLACENTA AND SPLEEN CRYOEXTRACTS, AS WELL AS THE CONDITIONED ENVIRONMENT OF MESENCHIMAL STEM CELLS

Introduction. Autoimmune hepatitis (AIH) is a chronic, relapsing, and remitting immune-mediated inflammatory disease of the liver. The global annual incidence of AIH is 1.4 per 100,000, with a prevalence of 17.4 per 100,000. The liver has a unique ability to regenerate in response to injury. The cell cycle of hepatocytes is a complex process that is tightly regulated by several well-coordinated mechanisms. Given the absence of a "gold standard" for the treatment of AIH, our attention has turned to studying the application of biotechnological preparations that do not contain cells subjected to low temperatures during their production (cryoextracts) or during long-term storage. The object of the study was selected as acellular cryopreserved biological products (ACBPs) of domestic production: cryoextract of placenta (CEP), cryoextract of spleen (CES), and conditioned medium from mesenchymal stem cells (CM-MSC). Aim. To characterize the effect of cryoextracts from placenta and spleen, as well as the conditioned medium of mesenchymal stem cells, on the cell cycle of hepatocytes in experimental autoimmune hepatitis. Materials and methods. AIH in rats was modeled by administering a hepatotropic antigenic mixture consisting of Freund’s complete adjuvant and a solution of antigen derived from the homogenate of allogeneic liver. Flow DNA cytometry was performed using a multifunctional flow cytometer "Partec PAS" (Partec, Germany). Results. It was found that in AIH, there is a statistically significant (p=0.007) decrease in the proportion of hepatocytes in the G0G1 phase of the cell cycle by 12.7%, against a backdrop of an increase in the proportion of cells in the S phase and in the G2M phase by 28.7% (p=0.037) and 13.0% (p=0.3), respectively, compared to the indices of intact rats. These changes in the ratio of hepatocytes across cell cycle phases led to a compensatory increase of 21.7% (p=0.08) in the proliferative index. Against the background of administering the reference preparation Silibor, a statistically significant (p=0.045) decrease in the proportion of hepatocytes with fragmented DNA (SubG0G1) by 18.3% was established compared to untreated animals with AIH. The study of the effect of ACBPs on the cell cycle of hepatocytes in AIH rats showed that in terms of reducing the proportion of cells with fragmented DNA, the investigated biotechnological preparations exceeded the effectiveness of the reference preparation Silibor. Conclusions. DNA cytometry indicated that the application of ACBPs led to the restoration of AIH-induced disturbances in the cell cycle of hepatocytes. It was established that in terms of the ability to reduce the proportion of hepatocytes with fragmented DNA (SubG0G1), the investigated ACBPs can be ranked by the percentage reduction in the number of hepatocytes with fragmented DNA relative to the indices of rats in the control group as follows: CM-MSC (71.2%; p<0.001) > CEP (50.0%; p<0.001) > CES (45.4%; p<0.001).