脂肪因子在间充质干细胞治疗骨关节炎中的效应及作用机制

项目名称： 脂肪因子在间充质干细胞治疗骨关节炎中的效应及作用机制

项目编号： No.81201404

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 卓奇

作者单位： 中国人民解放军总医院

项目金额： 23万元

中文摘要： 骨关节炎（OA）是中老年人群多发病和常见病，现有治疗以对症为主难以阻止病情发展。间充质干细胞（MSCs）如脂肪干细胞（ADSCs）是再生医学领域关节软骨等组织损伤修复最具潜力的细胞之一。近年来证据显示OA可能是一种系统性致病因素如代谢紊乱作为主要危险因素的疾病。白色脂肪组织分泌的脂肪因子可能是中间关键环节，也是目前国外研究代谢及炎症相关疾病新热点。我们构想脂肪因子通过影响关节微环境这一组织工程三要素之外的薄弱环节，对MSCs进行功能调控从而干扰其对OA的治疗效应。本研究拟采用分子、细胞、免疫学等方法对此进行初步论证，重点揭示瘦素、脂联素等脂肪因子在OA关节微环境中对ADSCs增殖、成软骨及旁分泌等关键指标的影响，分析探讨其作用模式与机制，同时建立改良的OA动物模型以探讨ADSCs在全身及局部脂肪因子高浓度环境下对OA的治疗效果，研究改善微环境的途径，为软骨再生及转化医学提供新思路。

中文关键词： 骨关节炎；脂肪干细胞；脂肪因子；细菌纤维素；再生医学

英文摘要： Osteoarthritis(OA), the most prevalent musculoskeletal disease in the senior population all over the world, is believed to long elude us in terms of its unsatisfactory treatment strategy. Therapeutic studies identified mesenchymal stem cells (MSCs) especially the readily attainable adipose-derived stem cells (ADSCs) are potentially one of the most promising candidates for cartilage repair, and the optimal intra-articular environment plays an underestimated but crucial role in cartilage regenerative medicine. Ever growing amount of evidence in recent years supports the theory that OA is more a systemic disease with metabolic disorders including obesity as its main risk factors. Further studies in this area proposed adipokines, a group of proteins secreted by adipose tissue, are deeply involved in the pathogenesis of the disease and potentially potent factors in the intra-articular environment to influence the efficiency of MSCs reparative capability. We aim to conduct in vitro molecular biological, cellular biological and immunological studies to investigate the impacts and the underlying mechanism of major adipokines (leptin and adiponectin) exerting on the proliferation, chondrogenesis and paracrine functions of ADSCs as well as on the morphological and functional features of novel cartilage. Additional animal

英文关键词： Osteoarthritis；Adipose-derived stem cells；Adipokines；Bacterial cellulose；Regenerative medicine