CXCR4-transduced bone marrow mesenchymal stem cells contribute to liver regeneration in cirrhotic rats through the transplant microenvironment

Bone marrow mesenchymal stem cells (BMSCs) have multi-potential differentiation capacities and can prevent the loss of hepatic parenchymal cells and promote tissue repair. However, the poor engraftment of BMSCs is one of the primary barriers to the effectiveness of this cell therapy. A previous study indicated that CXCR4 overexpression improved the repair ability of BMSCs by increasing the homing of BMSCs. In this study, we constructed lentiviral vectors expressing CXCR4, transduced these into BMSCs, and then investigated the potential mechanism of the contribution of CXCR4-BMSCs to liver regeneration. Our results showed that the regulation of CXCR4 expression influenced the directional homing of infused BMSCs at the early stage of cell transplantation and that nearly no BMSCs localized in the injured liver 72 h post-transplant. In addition, we found more PCNA expressing hepatocytes and more EpCAM and Jagged-1 expressing biliary duct cells in the livers of cirrhotic rats that underwent transplantation of CXCR4-BMSCs. This study indicated that CXCR4-mediated engraftment of BMSCs might enhance the interactions between the BMSCs and the hepatic progenitor cells in the transplant microenvironment, thus contributing to liver regeneration.