基质蛋白与整合素参与人骨髓间充质干细胞体外内皮的分化

Matrix proteins and integrin in the endothelial differentiation of human mesench ymal stem cells in vitro

目的:探讨基质蛋白与整合素在人骨髓间充质干细胞体外内皮分化过程中的作用,进一步明确其分化机制。方法:实验于2001-10/2003-03在吉林大学基础医学院病理生物学教育部重点实验室完成。采用不同基质蛋白纤维连接蛋白和Ⅰ型胶原,在诱导因子血管内皮细胞生长因子作用下对人骨髓间充质干细胞进行内皮诱导分化。通过免疫细胞化学和流式细胞分析检测分化标志和β1整合素。结果:纤维连接蛋白和Ⅰ型胶原组细胞诱导后可引起内皮分化早期标志KDR和CD34增强,纤维连接蛋白效应较为明显;两种基质蛋白也引起分化细胞β1整合素表达增强。结论:细胞外基质-整合素受体和血管内皮生长因子相互作用调控人骨髓间充质干细胞分化;人骨髓间充质干细胞诱导后具备内皮分化趋势;β1整合素的改变参与人骨髓间充质干细胞的内皮分化。该研究为寻找组织修复再生、心肌梗死和缺血性疾病治疗,以及血管组织工程的新型种子细胞提供了新的思路和方法。

AIM:To investigate the effect of matrix proteins and integrin on the endotheli al differentiation of human mesenchymal stem cells(hMSCs) in vitro and confirm t he differentiation mechanism further. METHODS:From October 2001 to March 2003,the experiment was performed in the Ke y Laboratory of Pathobiology,Ministry of Education,Basic Medical School of Jilin University.The combination of vascular endothelial growth factor 165(VEGF165) a nd various extracellular matrix(ECM) including matrix protein fibronectin(FN) an d type Ⅰcollagen(Col) was used to induce endothelial differentiation of hMSCs i n vitro.By using immunocytochemical method and flow cytometry,the differentiatio n marker and β1 integrin were detected. RESULTS:The early endothelial marker KDR and CD34 was expressed stronger after hMSCs were induced in both FN and Col groups,as compared with before induction, especially in the FN group.β1 integrin expression of induced population was enh anced strongly in both matrix proteins by VEGF induced differentiation of hMSCs . CONCLUSION:ECM integrin receptor and VEGF165 regulates differentiation of hMS Cs;the hMSCs are induced to have tendency of endothelial differentiation;the alt eration of β1 integrin is involved in the endothelial differentiation of hMSCs. The present study provides the strategy for new seed cells of vascular tissue en gineering,tissue repair and regeneration and therapies of ischemic disease and m yocardial infarction.