基底硬度变化下干细胞与肝内细胞间的相互作用影响其分化方向及细胞行为的力-化学机制探求

项目名称： 基底硬度变化下干细胞与肝内细胞间的相互作用影响其分化方向及细胞行为的力-化学机制探求

项目编号： No.11472001

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 黄岂平

作者单位： 重庆大学

项目金额： 88万元

中文摘要： 干细胞在治疗肝纤维化中的作用目前备受关注，然而对此过程中干细胞分化及行为却存在相互矛盾的报道。我们认为在基质硬度变化的前提下，干细胞与肝内细胞之间的相互作用，是影响干细胞分化方向和行为的关键因素，HGF，Wnt，TGF-b1-Smad，整联蛋白-RhoA，PI3K-Akt等信号亦起重要作用。这些力-化学信号可共同影响细胞收缩力而整合和互调，最终决定干细胞的分化和行为。为验证此假设，本项目拟利用牵引力显微镜和可磁力加载的微柱阵列研究不同基底硬度条件下，骨髓间充质干细胞与肝细胞、肝星状细胞间的相互作用，比较此过程中细胞收缩力的状态，以及干细胞分化状态与其细胞收缩力之间的关系，结合荧光蛋白FRET研究前述信号通路的激活和抑制与细胞收缩力变化之间的双向关系。本项目研究的开展可深化对干细胞分化行为以及其中力化学信号交互作用机理的认识，帮助找寻干细胞治疗肝纤维化的适宜力-化学条件，避免其负面作用的发生

中文关键词： 骨髓间充质干细胞；微柱阵列；细胞间粘附；力学信号转导；肝纤维化

英文摘要： The Therapeutic potential of stem cells in liver fibrosis have been paid more close attention currently; However, reports on the differentiation and behavior of stem cells in this process are still contradictory now. We believe that under the variation of matrix stiffness in liver, the interactions between stem cells and liver origin cells are the key factors which determine stem cells differentiation and other cell behavior in liver fibrosis. Meanwhile, signals pathway such as HGF，Wnt，TGF-beta1-Smads, integrins -RhoA, PI3K-Akt etc., also play important roles in this process. These mechanical-chemical signals can cross-talk between each other through the variation of cell contractility and result in being integrated, and then impact on the differentiation of stem cells consequently. To verify this hypothesis, this project intends to use traction force microscope and micropillars array which could be loaded by magnetic force to research interactions between bone marrow mesenchymal stem cells, hepatic cells and hepatic stellate cells; comparing the performance of cell contractility in those processes as well as the relationship between the state of stem cell differentiation and cell contractility; fluorescent protein FRET would be applied to investigate the mutual relationship between the activation or inhibition of those signals pathways aforementioned and the variation of cell contractility. As this project was carried out, it would help to deepen the understanding of the differentiation behavior of stem cells and the interaction mechanisms between mechanical and chemical signals in these process. Furthermore, it would help to develop suitable mechanical-chemical conditions for stem cells therapeusis of liver fibrosis, avoiding its negative effects as well

英文关键词： bone marrow mesenchymal stem cells;micropillars array;cell-cell adhesionm;echanical signal transduction;liver fibrosis