细胞外基质生物材料促进间充质干细胞体外增殖、分化及其调控机制的研究

项目名称： 细胞外基质生物材料促进间充质干细胞体外增殖、分化及其调控机制的研究

项目编号： No.51203194

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机高分子材料学科

项目作者： 何帆

作者单位： 苏州大学

项目金额： 25万元

中文摘要： 间充质干细胞生长所在的特定的微环境（壁龛）的外基质及各种分子对于干细胞的丰度和命运有重大影响。传统的细胞培养材料较难模拟正常间充质干细胞所需的复杂壁龛环境，因而影响到干细胞体外扩增能力、多次传代后的分化潜力。本项目针对目前细胞治疗与再生医学对于干细胞的需求，通过调控生物材料表面化学性质及细胞培养环境，诱导滑膜细胞在生物材料表面分泌特定的细胞外基质（ECM）；采用脱细胞技术及稳定化技术，在基本保存ECM生物活性物质成分的前提下，获取脱细胞的ECM生物材料；随后利用ECM生物材料对间充质干细胞进行体外培养，优化构建ECM条件，探讨ECM调控干细胞增殖和老化的机制，阐明ECM生物材料影响MSCs定向分化能力及其机理，初步验证ECM培养干细胞的应用安全性，开发一种高效的体外扩增干细胞技术。

中文关键词： 细胞外基质；间充质干细胞；自我更新；多向分化；生物安全性

英文摘要： Mesenchymal stem cells （MSCs） are considered as a promising source for tissue engineering and regenerative medicine because of their excellent capacities of self-renewal and multipotent differentiation. The conventional in vitro expansion system, however, limits the utilization of MSCs because in the monolayer culture MSCs rapidly loose their self-renewal ability and differentiation potentials, and result in cell senescence. Extracellular matrix （ECM） provides an essential microenvironment for MSCs and plays an important role in the cell adhesion, survival, migration, proliferation, differentiation and matrix remodeling. Therefore, reconstructing in vitro natural microenvironment for MSCs facilitates large-scale expansion of MSCs and maintains the stemness. In this proposal, we plan to generate a biomaterial based on decellularized ECM deposited by synovial cells and develop an in vitro MSC nich. Firstly, we will stimulate synovial cells to secrete ECM, and analyze its micro-structure and matrix components. Then we will use this decellularized ECM to expand MSCs in vitro, and study the influence of ECM on MSCs self-renewal capacity and cell senescence. Furthermore, we will compare the chondrogenic potential of MSCs expanded by ECM system to the traditional culture system, and analyze the mechanism of ECM regula

英文关键词： Extracellular matrix；mesenchymal stem cells；self-renewal；multilineage differentiation；biosafety