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

HC Ma, XL Shi, HZ Ren, XW Yuan… - World Journal of …, 2014 - pmc.ncbi.nlm.nih.gov
HC Ma, XL Shi, HZ Ren, XW Yuan, YT Ding
World Journal of Gastroenterology: WJG, 2014pmc.ncbi.nlm.nih.gov
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 …
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 mice were analyzed.
RESULTS
In vitro, CXCR4-MSCs showed better migration capability toward stromal cell-derived factor-1α and a protective effect against thioacetamide in hepatocytes. In vivo imaging showed that CXCR4-MSCs migrated to the liver in larger numbers than Null-MSCs 1 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-67 showed 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.
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