Effect of combined transplantation of multipotent mesenchymal stromal cells and stellate liver cells on the morpho-functional state of the liver after adminitration of CCL₄

Abstract

The aim of this study was to investigate the effect of combined transplantation of multipotent mesenchymal stromal and stellate liver cells on the morphofunctional state of the liver after toxic damage caused by carbon tetrachloride.
Objectives of the study:
1. To evaluate changes in liver morphometric parameters after combined administration of multipotent mesenchymal stromal cells (MMSC) and hepatic stellate cells (HSC) in toxic liver damage.
2. To study the effect of cotransplantation of MMSC and HSC on changes in blood biochemical parameters in toxic liver damage.
3. To investigate the activity of the DNA repair system after the introduction of MMSC and HSC in toxic liver damage.
Methods. The experiments were performed on 63 white laboratory male mice aged 7-8 mos. Toxic hepatitis was caused by intraperitoneal administration of carbon tetrachloride (CCl₄) at a dose of 50 µl/mouse. The mice were divided into experimental and control groups. Animals of the experimental group were injected into the lateral caudal vein with MMSCs obtained from the chorion of the placenta of female mice and with HCP at doses of 4 million cells/kg (120 thousand cells/mouse) and 9 million cells/kg (270 thousand cells/mouse), respectively, suspended in 0.2 ml of 0.9% NaCl solution. Animals of the control group were injected with 0.2 ml 0.9 % NaCl into the lateral caudal vein. Intravenous injections were performed 1 hr after the administration of carbon tetrachloride. Rats were administered with MMSCs of the third passage. Transplanted HSC had not been subjected to cultivation. The effect of combined MMSC and HSC transplantation on the morpho-functional state of the liver was studied on the 1st, 3rd, and 7th days after administration of carbon tetrachloride. Results. The combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells leads to an increase in the mitotic activity of hepatocytes, an increase in the number of binuclear hepatocytes, and an increase in the nuclear-cytoplasmic ratio. Administration of stem cells helps to reduce the programmed cell death of hepatocytes by increasing the activity of repair enzymes of the PARP family.