Use of mesenchymal stem cells to accelerate regeneration processes in acute toxic liver injury in an experiment

Abstract

Introduction. The impact of a complex chemical load on the population of the whole world, the use of pharmacological preparations, alcohol-containing products are the main factors that determine the high frequency and prevalence of toxic hepatitis. The search for new approaches for the treatment of toxic liver damage in order to restore structural and functional disorders is one of the urgent tasks of medicine. Of particular interest are the methods of regenerative medicine based on the use of various types of stem cells. Purpose of the study - study of the effect of transplantation of multipotent mesenchymal stem cells on the processes of regeneration in the liver of rats with induced acute toxic hepatitis. Materials and methods. An experimental study was conducted on 114 outbred male rats (3-5 months old) weighing 250-390 g. The animals were divided into 3 main groups. Group 1 - control animals (n=15). Group 2 (positive control) single intragastric injection of an oil solution of carbon tetrachloride (CCl4) at a dose of 1500 mg/kg (n=41); Group 3 (n=58) intragastrically injected with CCl4 at a dose of 1500 mg/kg, and intravenous transplantation of MMSC of 2×106, was carried out. On the 1st, 3rd, 5th, 7th day of the experiment as well as the collection of organs and tissues for histological and morphometric studies was made. Results. According to immunofluorescent analysis, intravenously transplanted MMSCs were found in the liver of rats at the 3rd and all subsequent periods of observation. In the present study, MMSC transplantation led to a statistically significant decrease in infiltrative processes in the liver tissue on the 3rd and 5th days of the study by 28.3% (p<0.0001) and 18.75% (p=0.0074) according to compared with the positive control group. On day 7, MMSC transplantation reduced the degree of fatty degeneration of the organ. The decrease in pathological manifestations of toxic hepatitis in rats is associated with an earlier activation of the mechanisms of reparative regeneration. Implementation of liver regeneration against the background of MMSC transplantation was carried out by enhancing protein-synthetic processes in liver cells, as well as increasing the mitotic activity of hepatocytes. Conclusions. The conducted experimental study showed that MMSC transplantation is an effective method of stimulating regenerative processes in the liver after its acute toxic damage. Limitations. In this experiment, lipid peroxidation processes in rat liver cells were not assessed, these criteria were not included in the study, and may be the subject of further study. Ethics. Work with laboratory animals was carried out with the approval of the bioethical committee of the North-Western State Medical University. I.I. Mechnikov dated November 11, 2020, as well as in accordance with the international GLP rules adopted in the Russian Federation (Rules for Good Laboratory Practice), Order No. 267 of the Ministry of Health of the Russian Federation dated June 19, 2003.