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

我们曾报道内皮祖细胞（EPC）移植可减轻肝纤维化，促进肝再生。在目前的研究中，我们调查的假设，基因转移可以用来实现表型调制的EPCs。特别是，我们研究了人肝细胞生长因子（hHGF）转导的EPCs在缺氧大鼠肝脏中的再生特性的影响。CCl_4处理后10周，AdhHGF组肝纤维化程度较AdLacZ组明显减轻。AdhHGF转染组Ki67阳性肝细胞明显增多。AdhHGF转染组血清总蛋白和白蛋白水平显著高于AdLacZ转染组。总之，这种通过hHGF转移增强移植的EPCs的再生加速将为严重的肝脏疾病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.