软骨调节素-I调控骨髓基质干细胞体内软骨形成

项目名称： 软骨调节素-I调控骨髓基质干细胞体内软骨形成

项目编号： No.31271046

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 曹谊林

作者单位： 上海交通大学

项目金额： 87万元

中文摘要： 由于缺乏理想的软骨移植供体，耳、鼻、气管等非关节部位软骨缺损的修复一直是外科治疗的难题。骨髓基质干细胞(BMSC)体外三维软骨构建的成功，为解决这一难题提供了可能。然而，BMSC再生的软骨在非关节环境中很容易丧失软骨表型和功能，严重阻碍了其向临床应用的转化。究其原因主要与血管化有关，解决问题的关键是抑制血管化。软骨调节素1(ChM-I)是维持软骨表型稳定最重要的抗血管化因子，但ChM-I能否用于调控BMSC异位软骨形成的稳定性尚不清楚。本项目将以预实验证实的ChM-I表达水平与构建软骨体内异位稳定性的关联为依据，通过ChM-I基因敲除及过表达小鼠BMSC构建软骨的体内外系统研究，深入阐明ChM-I调控BMSC体外软骨形成及体内异位稳定性的重要作用与机制，并以此为基础，进一步探讨ChM-I缓释技术提高BMSC构建软骨体内异位稳定性的可行性，以期为基于干细胞的组织工程软骨临床应用奠定基础。

中文关键词： 软骨调节素-1；间充质干细胞；组织工程软骨；异位稳定性；基因敲除小鼠

英文摘要： Due to poor regenerative capacity of cartilage in vivo, the repair of cartilage defects is always a great challenge in surgery therapy.The success of in vitro cartilage regeneration based on bone marrow stem cells(BMSCs) provides a promising approach for cartilage repair.However, the currently BMSC- engineered cartilage in vitro is unsatisfactory for clinical application due to ectopic ossification after subcutaneous implantation.It has been widely reported that endochondral ossification mainly results from angiogenesis and thus anti-angiogenesis becomes the major obstacle for clinical application of the BMSC-engineered cartilage. Chondromodulin-1(ChM-I), one of the anti-angiogenic factors during embryonic chondrogenesis, plays the most important role in maintaining the cartilage stability. But it remains unclear whether ChM-I could modulate the ectopic chondrogenesis in BMSC-based cartilage engineering. Our preliminary study has already showed that the ChM-I expression might be correlated with ectopic angiogenesis of BMSC-engineered cartilage. Based on the preliminary study, this research project will investigate the indispensability of ChM-I during BMSC-based cartilage engineering through the comparison of both in vitro construction and in vivo fate between the ChM-I knockout and widetype mice. Besides, this p

英文关键词： Chondromodulin-I；Mesenchymal stem cell；Cartilage tissue engineering；Ectopic stability；Gene knockout mouse