TGF-β1信号通路介导成纤维细胞促进移植肝细胞血管化的研究

项目名称： TGF-β1信号通路介导成纤维细胞促进移植肝细胞血管化的研究

项目编号： No.81470898

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李德卫

作者单位： 重庆医科大学

项目金额： 67万元

中文摘要： 肝细胞移植前景广阔，但血管化不足是移植肝细胞长期存活及增殖的主要障碍。作为肿瘤中最重要的微环境成分，成纤维细胞被肿瘤分泌的TGF-β1等细胞因子激活后对肿瘤新生血管的形成发挥至关重要的作用，故成纤维细有望成为解决肝细胞移植后血管化不足问题的重要媒介。本研究拟将TGF-β1基因修饰成纤维细胞，先通过体外及体内实验了解并证实TGF-β1途径激活的成纤维细胞具有促血管生成作用，再将TGF-β1基因修饰的成纤维细胞与胚胎肝细胞联合移植到SD大鼠肝脏。旨在通过了解TGF-β1信号与成纤维细胞激活的关系、激活的成纤维细胞表达HGF、COX-2、VEGF-A、SDF-1、MMP-9等促血管生成相关因子的情况、移植肝细胞的血管化情况，探讨TGF-β1途径介导成纤维细胞促进移植肝细胞血管化的作用及机制，为解决移植肝细胞长期存活及增殖困难奠定基础。

中文关键词： 转化生长因子；成纤维细胞；肝细胞移植；血管生成

英文摘要： The hepatocyte transplantation shows a promising prospect, however as the consequence of insufficient vascularization, it is difficult for transplanted hepatocyte to have long-term survival and proliferation. As the most crucial component in microenvironment of tumor, actived fibroblast, induced by cytokine such as TGF-β1 secreted by tumor, plays an important role in the process of neovascularization and proliferation in tumor cells. Given this, fibroblast can be regarded as a significant medium to solve the problem of insufficient vascularization after hepatocyte transplantation. This research is planned to modify fibroblast with TGF-β1 gene: conduct experiment in vitro and vivo to perceive and verify the function that the actived fibroblast, induced by TGF-β1, can stimulate angiogenesis; and then co-transplanted the fetal hepatic cells and fibroblasts, modified by TGF-β1 gene, into the liver of SD rats. By cognizing the relationship between TGF-β1 signaling and actived fibroblast, the condition actived fibroblast responding to factors which stimulate angiogenesis such as HGF,COX-2,VEGF-A,SDF-1 and MMP-9, and the vascularization of transplanted cells, the experiment is aimed to investigate the effect and mechanism of the activated fibroblasts induced by TGF-β1 signal pathway in the vascularization and proliferation of transplanted liver cells, to lay a foundation as to solve the difficulty in terms of long-term survival and proliferation of transplanted hepatocyte.

英文关键词： Transforming growth factor;Fibroblast;Hepatocyte transplantation;Vascularization