Development of liver regeneration therapy using of anti-fibrotic gene-modified endothelial progenitor cells

先前我们曾报道内皮祖细胞(EPC)移植可以减轻已形成的肝纤维化，促进肝再生。在目前的研究中，我们研究了基因转移可以实现内皮祖细胞表型调节的假设。特别是，我们研究了转导人肝细胞生长因子(HHGF)的内皮祖细胞在肝硬变大鼠肝脏中对再生特性的影响。在CCl_4治疗后10周，AdhHGF转导组的肝纤维化程度明显低于AdLacZ转导组。转导AdhHGF组Ki67阳性肝细胞明显增多。AdhHGF转导组的血清总蛋白和白蛋白水平明显高于AdLacZ转导组。综上所述，通过hHGF转移促进移植内皮祖细胞的再生，将为重症肝硬变患者的肝再生提供新的治疗策略。

Previously we reported that endothelial progenitor cell (EPC) transplantation could reduce established liver fibrosis and promote hepatic regeneration. In the current study, we investigated the hypothesis that gene transfer can be used to achieve phenotypic modulation of EPCs. Especially, we investigated the effect on regenerative properties of human hepatocyte growth factor (hHGF)-transduced EPCs in cirrhotic rat liver. In AdhHGF-transduced group, the degree of liver fibrosis was suppressed compared to those in AdLacZ-transduced group at 10 weeks after CCl_4 treatment. Ki67-positive hepatocytes in AdhHGF-transduced group were significantly increased. Moreover, serum total protein and albumin levels were significantly higher in AdhHGF-transduced group than those in AdLacZ-transduced group. In conclusion, this enhanced regenerative acceleration of transplanted EPCs by hHGF transfer will provide novel therapeutical strategy for hepatic regeneration in severe cirrhotic liver disease patients.