Therapeutic Effects of CXCL9-overexpressing Human Umbilical Cord Mesenchymal Stem Cells on Liver Fibrosis in Rats

Abstract

\n Background: Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation have become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver sites appears to be poor. In this study, we aimed to determining if overexpression of CXCL9 could have the synergistic anti-fibrosis effect with UC-MSCs, and whether it can promote the homing ability of UC-MSCs.Methods: Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfection of naive UC-MSCs with the lenti-CXCL9-mCherry. The impact of transplanted CXCL9-UC-MSCs on both repairing of liver fibrosis and homing was evaluated and compared with lenti-mCherry empty vector transfected UC-MSCs (control UC-MSCs).Results: After puromycin screening, UC-MSCs could stably express CXCL9 without affecting the stem and differentiation ability of UC-MSCs. In addition, biochemical analysis showed that the liver function of CXCL9-UC-MSCs was significantly increased in comparison with that of control UC-MSCs (P < 0.05). Futhermore, histopathology after 4 weeks of cell therapy demonstrated that the content of collagen fibers decreased obviously, the pseudo-lobules almost disappeared, and the morphology of hepatic lobules was basically normal. Frozen sections were performed 24 hours and 4 weeks after the cell injection. It can be seen that the fluorescence expression of the CXCL9-UC-MSCs group was significantly higher than that of the control UC-MSCs group, which proved that CXCL9-UC-MSCs have a stronger chemotactic ability, and can stay longer than control UC-MSCs in the injured liver.Conclusion: Overexpression of CXCL9 improves the efficacy of UC-MSC therapy for liver fibrosis repair, thereby promoting the homing and staying of UC-MSCs to injured hepatic sites in a rat model of liver fibrosis.