Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration

AIM:To improve the colonization rate of transplanted mesenchymal stem cells(MSCs)in the liver and effect of MSC transplantation for acute liver failure(ALF).METHODS:MSC was modified with the chemokine CXC receptor 4(CXCR4)gene(CXCR4-MSC)or not(Null-MSC)through lentiviral transduction.The characteristics of CXCR4-MSCs and Null-MSCs were determined by real-time quantitative polymerase chain reaction,Western blotting and flow cytometry.CXCR4-MSCs and Null-MSCs were infused intravenously 24 h after administration of CCl4 in nude mice.The distribution of the MSCs,survival rates,liver function,hepatocyte regeneration and growth factors of the recipient micewere analyzed.RESULTS:In vitro,CXCR4-MSCs showed better migration capability toward stromal cell-derived factor-1αand a protective effect against thioacetamide in hepatocytes.In vivo imaging showed that CXCR4-MSCs migrated to the liver in larger numbers than Null-MSCs1 and 5 d after ALF.Higher colonization led to a longer lifetime and better liver function.Either CXCR4-MSCs or Null-MSCs exhibited a paracrine effect through secreting hepatocyte growth factor and vascular endothelial growth factor.Immunohistochemical analysis of Ki-67showed increased cell proliferation in the damaged liver of CXCR4-MSC-treated animals.CONCLUSION:Genetically modified MSCs expressing CXCR4 showed greater colonization and conferred better functional recovery in damaged liver.

AIM: To improve the colonization rate of transplanted mesenchymal stem cells (MSCs) in the liver and effect of MSC transplantation for acute liver failure (ALF).