iPSC-MSCs复合活性大孔CPC用于牙槽骨缺损修复及转归机制的研究

项目名称： iPSC-MSCs复合活性大孔CPC用于牙槽骨缺损修复及转归机制的研究

项目编号： No.81470722

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： 刘钧

作者单位： 四川大学

项目金额： 73万元

中文摘要： 较大范围牙槽骨缺损的修复是口腔临床亟待解决的难题，骨组织工程的发展为其提供了全新的思路和方法。骨再生包括三个关键要素：种子细胞、支架和诱导分化策略。课题组前期研究发现新兴种子细胞iPSC-MSCs比BM-MSCs更具骨再生潜能，并成功制备一种新型大孔磷酸钙骨水泥(CPC)支架材料；miRNA是近年干细胞组织工程新的强有力诱导手段，最新文献报道特定miRNA可同时促进BM-MSCs成骨分化及血管化。目前尚未见miRNA诱导人iPSC-MSCs进行骨再生的报道。本项目拟在前期研究基础上，使用新型大孔生物活性RGD-CPC为支架，接种iPSC-MSCs为种子细胞，从已知骨再生相关的重要miRNAs中挑选并转染iPSC-MSCs的最优miRNA，针对大鼠牙槽骨缺损进行修复研究，并探索特定miRNA对细胞增殖、分化的调控作用机制。结果可望为牙槽骨缺损修复提供理论和实验依据。

中文关键词： 骨再生；间充质干细胞；牙槽骨缺损

英文摘要： The repair of critical-sized alveolar bone defects remains a major challenging health issue in clinical dentistry worldwide. Bone tissue engineering using scaffolds and stem cells with induction methods provides a new promising approach for bone repair. Our research group recently found that mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs), a new type of progenitor cells, had a great potential to regenerate bone tissue with more efficiency compared with BM-MSCs. Moreover, we fabricating a novel macroporous biofunctionalized calcium phosphate cement (CPC) scaffold. The CPC scaffold had good mechanical strength for craniofacial bone repair applications and the seeding cells attached and grew well on it. Recently, microRNAs (miRNAs) have become an important tool to induce both osteogenic and angiogenic differentiation of stem cells simultaneously in the field of tissue engineering. However, to date there has been no report on miRNA regulation of human iPSC-MSC for bone regeneration. Moreover, only a few investigations have investigated the mechanism of miRNA regulation of osteogenic differentiation. The present project will seed human iPSC-MSCs on the novel macroporous CPC biofunctionalized with Arg-Gly-Asp (RGD) (referred to as RGD-CPC) for repair of rat critical-sized alveolar bone defects. The key miRNA(s) related with both iPSC-MSC osteogenesis and angiogenesis will be selected and iPSC-MSCs will be induced by miRNA gene modification. The project will investigate the effects and mechanisms of miRNA regulation of iPSC-MSC proliferation and differentiation. The project will hopefully provide theoretical and experimental supports for alveolar bone defect repair.

英文关键词： bone regeneration;mesenchymal stem cells;alveolar bone defect