Mesenchymal Stromal Cells Suppress Hepatic Fibrosis Via Modulating the Expression of Fibronectin and Integrin and Inhibiting DNA Fragmentation in Rats

Abstract

Introduction: Liver fibrosis is currently the 11th most common cause of death worldwide. Because of self-renewal, available sources for isolation, and high differentiation properties, multipotent mesenchymal stromal stem cells are suggested to be potential tool for treatment of liver fibrosis. In this study, we examined the anti-fibrotic and anti-inflammatory activity of bone marrow-derived multipotent mesenchymal stromal stem cells (MSCs) on liver fibrosis induced by carbon tetrachloride on rats relative to silymarin as a standard drug.

Material and methods: This study was performed on 40 male Sprague Dawley rats divided into 4 groups of ten rats each: Group 1 served as controls, Group 2 served as CCl4 (diseased) group, Group 3 served as silymarin treated group and Group 4 served as MSCs treated group. Liver fibrosis was assessed by determination of liver markers and fibrogenesis related genes together with the anti-inflammatory markers in the liver tissue. DNA fragmentation was assessed by Comet assay.

Results: MSCs treatment reduced all liver fibrosis markers as well as the oxidative stress and inflammatory markers. Additionally, MSCs reduced the expression of integrins and fibronectin compared with the control group as well as decreasing DNA fragmentation.

Conclusions: Treatment by MSCs significantly ameliorates liver fibrosis in rats. This amelioration was a result of acting on both the anti-inflammatory and anti-fibrotic activity of hepatocytes.