中国肿瘤生物治疗杂志2017，Vol.24Issue(6)：595-600,6.DOI:10.3872/j.issn.1007-385X.2017.06.004
人脐带来源间充质干细胞向HepG2肝癌细胞原位移植瘤的归巢及分化
Tropism and differentiation of human umbilical cord derived mesenchymal stem cells to tumor transplanted by hepatocarcinama HepG2 cells in situ
摘要
Abstract
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.关键词
间充质干细胞/肝癌/归巢/分化Key words
mesenchymal stem cells(MSC)/hepatocarcinoma/tropism/differentiation分类
医药卫生引用本文复制引用
范冬梅,张子祥,赵英新,杨铭,张砚君,颜次慧,蒋媛,吕军强..人脐带来源间充质干细胞向HepG2肝癌细胞原位移植瘤的归巢及分化[J].中国肿瘤生物治疗杂志,2017,24(6):595-600,6.基金项目
国家自然科学基金资助项目(No.81400176,No.81402121) （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). Supported by the National Natural Science Foundation of China(No.81400176,No.81402121),and the Foundation for Applied Research and Advanced Technology of Tianjin (No.14JCYBJC23700) （No.14JCYBJC23700）
