Possibility of using combined transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells to activate reparative liver regeneration in mature and old organism

Victoria Vakhrusheva,Ekaterina Petrunina,Irina Maklakova,Dmitry Grebnev

doi:10.1051/bioconf/20202201004

Victoria Vakhrusheva, Ekaterina Petrunina + Show 2 more

Open Access

https://doi.org/10.1051/bioconf/20202201004

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Abstract

The aim of the study was to examine the effect of combined transplantation of multipotent mesenchymal stromal (MMSC) and hepatic stellate (HSC) cells on liver regeneration after resection. Research has been carried out on laboratory animals of mature and old age. After the subtotal resection of the liver, MMSC and HSC were introduced in the tail vein in the amount of 4 million cl/kg of body weight and 9 million cl/kg of body weight respectively. Evaluation of reparative liver regeneration was performed on the 1st, 3rd, 7th days after subtotal liver resection. Features of reparative liver regeneration in mature and old organism were revealed. In mature organism against the background of combined cell transplantation, regeneration activation is achieved by increasing cellular and intracellular regeneration mechanisms. In this case, the old organism responds to cell transplantation by activating only intracellular mechanisms. In both age groups, decreased mutagenesis and inhibition of programmed cell death against the background of MMSC cotransplantation and HSC were observed.

Highlights

Finding alternative ways to activate liver regeneration under conditions of its damage in aging is a pressing problem
It is known that compensatory-adaptive capabilities, cells ability to homing, differentiation - all of it is decreased in the old organism, which determines significant changes in the rate of reparative regeneration [1, 2, 3]
When studying morphometric liver parameters on the 1st day after liver resection in mature and old laboratory animals on the combined mesenchymal stromal cells (MMSC) and hepatic stellate cells (HSC) transplantation background, a decrease in apoptotic index compared to the control subgroups was found

Summary

Introduction

Finding alternative ways to activate liver regeneration under conditions of its damage in aging is a pressing problem. Because of their ability to produce biologically active substances and their immunomodulatory characteristics, MMSC introduction is considered a promising solution for acute hepatic insufficiency therapy [5, 6]. A significant role in liver regeneration is given to hepatic stellate cells (HSC). These cells form the microenvironment of hepatocytes, forming collagen (IV, VI, XIV types), glycoproteins, proteoglycans. Given the biological features of the interaction between MMSC and HSC, it seems promising to use combined MMSC and HSC transplantation to activate liver regeneration after its subtotal resection

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