项目名称： 不同发育起源MSCs在骨缺损修复重建过程中的作用及机制研究

项目编号： No.81501901

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 翟志臣

作者单位： 中山大学

项目金额： 18万元

中文摘要： MSCs发育起源不一所致细胞群体异质性制约了其在组织工程骨中的应用效果，而不同MSCs亚群因缺乏特异性表面标志而难以分选。本研究拟从发育角度解决这一问题，将iPS细胞经胚体分别向神经嵴和中胚层诱导，进而分离得到两种发育起源的MSCs。然后通过：一、在细胞水平上比较两种起源MSCs的增殖与分化性能及表面标志差异；二、与脱细胞松质骨支架复合，比较组织工程骨体外构建情况下两种起源MSCs在支架中的粘附、增殖、成骨分化与骨基质分泌情况；三、将细胞支架复合体植入构建的动物骨缺损模型，通过荧光标记体内示踪，观察两种起源MSCs在体内组织工程骨重建过程中的存活迁移情况，于术后各时间评价骨修复效果，分析外源MSCs的分布及新生骨组织的来源，研究两种起源MSCs在体内外骨重建中的作用机制。本研究将为解决MSCs的异质性，阐明不同亚群MSCs在骨重建中的作用提供新思路，有助于指导MSCs在组织工程骨中的应用。

中文关键词： 骨重建；组织工程；诱导多能干细胞；间充质干细胞；细胞亚群

英文摘要： The heterogeneity of MSCs caused partly by variety of progenitors hinders the application effects of tissue-engineered bone, while it’s difficult to sort out distinct MSCs subsets due to the lack of specific surface markers. This research aims to solve this problem from a new development point of view. iPS cells will be respectively induced to nerual crest and mesoderm through embryo body, and MSCs with these two origins can be got by further induction. Through: 1, comparing the cell proliferation, differentiation and surface markers of MSCs with two different origins; 2, seeding cells in xenogeneic cancellous bone scaffolds to compare the adhering, proliferation, osteodifferentiation and matrices secretion of MSCs with two different origins during in vitro tissue-engineered bone regeneration; 3, implanting scaffolds seeded with MSCs into segmental bone defects, to observe the livability and migration of MSCs with different origins via fluorescence tracing in vivo; then evaluating bone repair effect after operation to analyze the distribution of exogenous MSCs and the source of neonatal bone tissue, finally illuminating the functional mechanisms of different MSCs origin on bone regeneration. This study will provide a new view to solve the heterogeneity of MSCs and to illustrate the function of different MSCs subsets during bone regeneration; and it will help to guide clinical application of MSCs for tissue-engineered bone.

英文关键词： Bone regeneration;Tissue engineering;iPS;MSCs;Cell subsets