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Vol. 24, Art. 39 (pp. 516-527)    |    2023       

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Experimental evaluation of the treatment effectiveness of mesenchymal stem cells in acute toxic hepatitis

Trapeznikova E.G., Shilov V.V.

1Research Institute of Hygiene, Occupational Pathology and Human Ecology Federal State Unitary Enterprise, Federal Medical Biological Agency
2North-Western State Medical University named after I.I. Mechnikov

Brief summary

Currently, the treatment of diseases of the hepatobiliary system of toxic origin is one of the most difficult problems of modern medicine. Acute hepatitis plays a leading role in the pathogenesis of toxic lesions. Despite the wide range of therapeutic measures and pharmacological schemes used to treat toxic liver damage, there is a high risk of disability and mortality in patients due to the unpredictability of the course of the inflammatory process, as well as the imperfection of the approaches used. The introduction of stem cell transplantation into clinical practice has made it possible to discover a fundamentally new approach to the treatment of many diseases. In toxicological practice, the methods of regenerative medicine are not currently widely used, although in some areas of medicine this method is one of the most effective. In order to expand the use of cellular technologies in medicine, experimental and clinical studies are needed to determine the safety and effectiveness of stem cell transplantation in diseases caused by exposure to various toxicants, the results of which will determine the prospects for their further use in this field. The purpose of the study was to experimentally evaluate the therapeutic efficacy of mesenchymal stem cells in acute toxic hepatitis in rats. To simulate acute toxic hepatitis in outbred rats, a single intragastric administration of carbon tetrachloride at a dose of 1500 mg/kg was performed. The culture of mesenchymal stem cells for intravenous transplantation was obtained from mouse embryonic stem cells by directed differentiation. To study the distribution of mesenchymal stem cells in the body of rats, before intravenous injection, cell membranes were stained with fluorescent dye RKH-26. The concentration of transplanted mesenchymal stem cells was 2×106 per animal. The results of the study indicate that MMSC transplantation to intact rats did not cause external signs of intoxication and did not lead to the death of animals for all periods of observation. After injection of mesenchymal stem cells suspension against the background of induced acute toxic hepatitis, a decrease in animal mortality was observed. The study of the distribution of mesenchymal stem cells in the body of rats after their systemic administration showed that the transplanted cells were found in the liver tissue on the 3rd and all subsequent periods of observation. This fact proves the migration of transplanted mesenchymal stem cells directly to the damaged organ, and also indicates the safety of the procedure.


Key words

regenerative medicine; pilot study; acute toxic hepatitis; multipotent mesenchymal stem cells; distribution; survival

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