Co-transplantation of endothelial progenitor cells and hepatocyte stem cells launches a counterattack against liver fibrosis in rats / 中国组织工程研究

ABSTRACT

BACKGROUND: At present, the transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) or bone marrow-derived hepatocyte stem cells (BDHSCs) is common in the treatment of liver fibrosis, but the combined treatment for liver fibrosis is rarely reported. Combined transplantation of BM-EPCs possessing the function of angiogenesis and BDHSCs possessing the function of hepatocyte regeneration might play a dual anti-fibrosis role. OBJECTIVE: To evaluate the reversal effect on liver fibrosis by the combined transplantation of BM-EPCs and BDHSCs in rats. METHODS: The liver fibrosis rat models were induced with CCl4 subcutaneous injections for 6 weeks. BM-EPCs of rats with liver fibrosis were obtained by culture induction in vitro.BDHSCs of rats with liver fibrosis were obtained by magnetic bead cell sorting.BM-EPCs and/or BDHSCs were transplanted into liver fibrosis rats via the tail vein and branch of the portal vein,and then the effects of BDHSCs transplantatiron on liver fibrosis and liver function were observed. RESULTS AND CONCLUSION: (1) Masson staining results showed transplantations of BDHSCs and BM-EPCs, alone or both, could suppress the formation of collagen fibers. However, the staging scores of liver fibrosis showed that only the combined transplantation of BM-EPCs and BDHSCs could significantly improve liver fibrosis,which was significantly different from the model group(1.75±0.25 vs. 3.00±0.19, P < 0.05). (2) The liver biochemical assay in the blood showed that the levels of all five parameters of alanine aminotransferase, aspartate aminotransferase, total bilirubin, prothrombin time, and activated partial thromboplastin time in the BM-EPCs/BDHSCs group were significantly improved to be equivalent to normal levels, compared with those in the model group (P < 0.05). To conclude, it is an effective treatment for liver fibrosis by the co-transplantation of BM-EPCs and BDHSCs.