Effect of MMSC and HSC on reparative regeneration of the liver under conditions of its toxic damage
I.Yu. Maklakova 1, 2, V.V.Bazarnyi 1, D.Yu. Grebnev 1, 2
1 Ural State Medical University of the Ministry of health of Russia,
Yekaterinburg, Russian Federation;
2 Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation
The aim of this study was to study the effect of combined MMSC and HSC transplantation on liver regeneration under conditions of toxic carbon tetrachloride damage.
Materials and methods. The study was performed on white male mice with toxic liver damage by intraperitoneal administration of carbon tetrachloride at a dose of 50 µl per mouse once. An hour after modeling liver damage, placental MMSCs and HSCs were administered intravenously at a dose of 4 million cells/kg and 330 thousand cells/kg, respectively, suspended in 0.2 ml of 0.9% NaCl solution. Control group animals were given 0.9% NaCl solution-0.2 ml intravenously. On days 1, 3, and 7 after cell transplantation, changes in inflammatory activity in the liver were evaluated, and mitotic and apoptotic indices were determined. On the 7th day after the introduction of cells, the activity of DNA repair enzymes of the PARP family was analyzed. Results. Combined MMSC and HSC transplantation leads to a decrease in the index of inflammatory activity in the liver due to a decrease in necrosis, hepatocyte dystrophy, and a decrease in infiltration. As a result of the study, an increase in the activity of PARP repair enzymes was found, which led to a decrease in programmed cell death. Also, cotransplantation of MMSCs and HSCs was accompanied by increased mitotic activity of hepatocytes. Conclusion. Cotransplantation of MMSCs and HSCs under conditions of toxic liver damage reduces the inflammatory response, stimulates the mitotic activity of hepatocytes, and increases the activity of enzymes of the DNA repair system. Activation of the liver's reparative system, in turn, reduces the programmed death of hepatocytes.
Keywords:multipotent mesenchymal stromal cells, hematopoietic stem cells, toxic hepatitis, reparative liver regeneration
There is no conflict of interest.
Contact details of the corresponding author:
Dmitry Yu. Grebnev
Received 03.12.2020
For citation:
Maklakova I.Yu., Bazarny V.V., Grebnev D.Yu. Effect of MMSC and HSC on reparative regeneration of the liver under conditions of its toxic damage. Url: http://vestnikural.ru/article/1143 [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2020, Vol. 17, no. 3, pp. 243–248. DOI: 10.22138/2500-0918-2020-17-3-243-248 (In Russ)
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Authors
Irina Yu. Maklakova
Ural State Medical University
Candidate of Medical Sciences, Associate Professor of the Department of pathological physiology
Russian Federation, 620028 Yekaterinburg, st. Repin 3
Institute of Medical Cell Technologies
Senior researcher
Russian Federation, 620026 Yekaterinburg, st. Karl Marx 22a
Vladimir V. Bazarnyi
Ural State Medical University
MD, PhD, Professor of the Department of clinical laboratory diagnostics and bacteriology
Russian Federation, 620028 Yekaterinburg, st. Repin 3
Dmitry Yu. Grebnev
Ural State Medical University
PhD, head of the Department of pathological physiology
Russian Federation, 620028 Yekaterinburg, st. Repin 3
Institute of Medical Cell Technologies
Senior researcher
Russian Federation, 620026 Yekaterinburg, st. Karl Marx 22a