HIF-1α调控CSPCs归巢分化促进体内不同环境软骨再生的研究

项目名称： HIF-1α调控CSPCs归巢分化促进体内不同环境软骨再生的研究

项目编号： No.81471878

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： 刘凯

作者单位： 上海交通大学

项目金额： 72万元

中文摘要： 软骨缺损修复一直是临床多学科面临的难题，传统以干细胞为主的软骨组织工程在一定程度上实现了软骨修复，但仍存在许多缺点。软骨原位再生通过激活自体干细胞迁移聚集向缺损区归巢分化，实现软骨原位再生，其中，CSPCs的归巢分化对软骨缺损的修复可能起着关键作用。然而，干细胞靶向归巢率偏低,影响了其作为干细胞疗法的效果。研究表明，HIF-1α表达增加可促进干细胞的归巢分化。因此，我们欲通过调节HIF-1α来控制CSPCs等干细胞归巢分化促进体内不同环境软骨再生。首先，通过过表达和干扰HIF-1α的方法，研究HIF-1α表达与CSPCs等干细胞体外迁移分化能力的关系；其次，将负载HIF-1α激活剂或拮抗剂的水凝胶植入软骨缺损区，评价HIF-1α的表达和CSPCs等细胞归巢、软骨修复的关系；最后，研究原位或异位骨膜/软骨膜和皮下软骨再生，探索HIF-1α调控CSPCs等干细胞归巢在不同环境下软骨再生的机制。

中文关键词： 低氧诱导因子-1；软骨干细胞；软骨；组织工程；微环境

英文摘要： The repair of cartilage defects has been always a multiple disciplinary problem, the traditional stem cell based therapy repair the cartilage defects to a certain degree, followed by the disadvantages: sophisticated medical treatments, low safety, an unstable cartilage phenotype, and so on. In situ cartilage regeneration promotes stem cells migrate to defects and differente into chondrocytes to repair the cartilage defects, and the homing and differentiation of CSPCs plays a key role in the process. Studies show that increased expression of HIF-1α promotes stem cell homing and differentiation. Therefore, we expect to promote cartilage regeneration in different environments in vivo by regulating HIF-1α expression in CSPCs. First, we plan to study the relationship between HIF-1α expression and migration and differentiation of CSPCs and other stem cells; Secondly, hydrogel loaded with HIF-1α activators and antagonists were injected into cartilage defects at different regions in order to evaluate the relationship among HIF-1α expression, stem cell homing and cartilage repair; Finally, in order to study the feasibility and mechanisms of CSPCs-based cartilage regeneration in different environments in vivo regulated by HIF-1α expression, hydrogel loaded with HIF-1α activators and antagonists were impanted into In situ and ectopic periosteum perichondrium and subcutaneously.

英文关键词： HIF-1α;cartilage stem/progenitor cell;cartilage;tissue engineering;microenvironment