表达HGF的骨髓间充质干细胞促进小移植肝早期肝再生

目的 建立大鼠小体积肝移植模型,输注表达人肝细胞生长因子(human hepatocyte growth factor,hHGF)的骨髓间充质干细胞(mesenchymal stem cells,MSCs),研究其在移植早期对小移植肝促再生作用.方法 将已建立的表达hHGF和绿色荧光蛋白(green fluorescence protein,GFP)的MSCs,分别命名为HGF/MSCs,GFP/Mscs.建立大鼠30%肝移植模型.受体分为4组,实验组输注5×106HGF/MSCs;对照组则分别输注相同体积的生理盐水(PS),5×106 GFP/MSCs或1.0×109 pfu含hHGF的重组腺病毒液(Ad-HGF).分别于术后1,3,5,7 d各组随机抽取5只大鼠处死.取血检测血清ALT和hHGF.记录移植物湿重.取肝组织检测hHGF、c-met表达,以及肝细胞凋亡和增殖活性.另每组15只,分组同上,用于观察生存期.结果 PS组大鼠7 d生存率33.3%;组织学及血清学检查示术后肝脏损伤重,汇管区单核细胞浸润多;而实验组大鼠7 d生存率为73.3%.肝脏损伤轻,炎性细胞浸润少;实验组移植肝再生较PS组明显增加.结论 大鼠部分肝移植后,输注HGF/MSCs能够保护小体积移植肝,促进小移植肝再生,提高7 d生存率.

Improvement of small-for-size liver graft regeneration by bone marrow-derived mesenchymal stem cells over-expressing hepatocyte growth factor

Objective To determine whether HGF-expressing MSCs will improve small-for-size liver grafts regeneration after liver transplantation.Methods The HGF cDNA was amplified from the exprcssion plasmid pCMV-HGF by PCR and subcloned into the same site of the plasmid pDC316- IRES-EGFP vector.Virus Ad-HGF was produced by homologous recombination.BM-MSCS were cul-tured and transduced with Ad-HGF.HGF/MSCs were generated.We implanted HGF/MSCs into liv-er grafts via the portal vein using a 30% small-for-size rat liver transplantation model.HGF,c-met expression,hepatic injury and liver regeneration were assessed after liver transplantation.Results The HGF-expressing MSCs improved liver function and liver weight recovery during the early post-transplantation period,resulting in a reduced mortality in rats after small-for-size liver transplanta-tion.Conclusions The MSCs genetically modified to Over-expressing HGF and implanted in the liver graft may offer a novel approach to promoting liver regeneration after small-for-size transplantation.