目的：观察人脐带来源的间充质干细胞（human umbilical cord derived mesenchymal stem cell，HUMSC）向HepG2肝癌细胞原位移植瘤的归巢及分化。 方法：二步法体外诱导HUMSC向肝细胞分化，通过Realtime PCR和Western blotting检测不同时间点HUMSC中肝细胞特异性基因甲胎蛋白（alphafetoprotein，AFP）及白蛋白（albumin，ALB）mRNA和蛋白水平的变化;Transwell实验观察HUMSC在HepG2肝癌细胞条件培养基作用下的趋化现象;采用皮下原位移植的方法建立BALB/c裸鼠的HepG2肝癌细胞原位移植瘤模型，利用慢病毒感染的方法将HUMSC标记CMV或AFP启动子驱动的fLuc，制备成MSC.CMVLuc或MSC.AFPLuc，并将其注射入荷瘤肝组织，IVIS成像系统观察MSC.CMVLuc向肿瘤部位的迁移归巢及MSC.AFPLuc在肝癌微环境中向肝细胞分化。 结果：HUMSC在体外诱导培养过程中出现细胞形态学变化证明其向肝细胞分化,同时诱导培养后AFP、ALB mRNA和蛋白的表达明显升高（均P<0.05）;HUMSC向HepG2肝癌细胞的趋化呈瘤细胞密度依赖性(P<0.01)；MSC.CMVLuc注射后2 d迁移并聚集于肝脏,注射后5 d肝脏内发光信号进一步增强；MSC.AFPLuc肝内注射后24 h已向肝细胞分化，注射第7天AFP启动子活性最强，注射第9天活性消失。结论：在小鼠体内外证明了HUMSC具有向肝脏归巢及分化的能力，为今后MSC应用于肝癌基因靶向治疗提供了一种新的策略。

Objective:To study the tropism and differentiation of human umbilical cord derived mesenchymal stem cell (HUMSC) to HepG2 orthotopic hepatocarcinoma. Methods: The in vitro hepatic differentiation of HUMSCs was induced by a twostep protocol; the changes in mRNA and protein expression of hepatic alphafetoprotein (AFP) and albumin (ALB) at different time points were examined by Realtime PCR and western blotting; the tropism of HUMSCs stimulated by conditional culture medium with HepG2 cells was identified by transwell assay. Subcutaeousorthotopic transplantation was used to build the HepG2 orthotopic hepatocarcinoma model in athymic BALB/c nude mice. HUMSCs were labeled with MSC.CMVLuc or MSC.AFPLuc through lentivirus transduction before orthotopically injected into hepatic parenchyma; the tropism of MSC.CMVLuc to tumor location as well as the hepatic differentiation of MSC.AFPLuc in tumorbearing liver was monitored by using IVIS living imaging system. Results：The in vitro hepatic differentiation of HUMSCs was successfully induced in vitrowith morphological changes, and the mRNA and protein levels of AFP and ALB significantly elevated after the culture (P<0.05); the tropism of HUMSCs to HepG2 cells was in a dosedependent manner (P<001). MSC.CMVLuc, which injected intravenously, migrated to liver after 48 h; and the luciferase signal in the liver of rats was enhanced on day 5. MSC.AFPLuc developed hepatic differentiation after 24 h of in situ transplantation; at day 7 of posttransplantation, the activity of AFP promoter was at the highest, while, its activity was undetectable at day 9. Conclusion：It was confirmed the tropism and differentiation of HUMSCs to liver by in vitro and in vivo experiments. This study may provide a new strategy of target gene therapy for hepatocarcinoma by using MSCs.

国家自然科学基金资助项目（No.81400176，No.81402121）;天津市应用基础与前沿技术研究计划基金资助项目（No.14JCYBJC23700）