人脐血非限定性干细胞对骨性关节炎动物模型的治疗作用

项目名称： 人脐血非限定性干细胞对骨性关节炎动物模型的治疗作用

项目编号： No.81472141

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： 朱红文

作者单位： 天津市天津医院

项目金额： 72万元

中文摘要： 骨性关节炎是临床常见疾病，但目前临床上缺乏有效治疗手段。本研究的目标是在骨性关节炎的早中期通过干细胞治疗修复软骨损伤和减轻炎性反应。前期的早期研究发现脐血中一种特殊细胞类型--非限定性体细胞干细胞（USSC）可通过释放细胞因子，替代缺陷细胞和免疫调控等方式促进创伤性和遗传性疾病的皮肤的愈合。USSC在体外还可诱导成为软骨细胞。我们的合作者目前已经具备可直接投入临床治疗的USSC。本课题将利用已建立的家兔骨性关节炎的动物模型来研究USSC治疗骨性关节炎的效用，以及探索最佳治疗方案包括细胞植入的时间节点，方式以及与全脐血细胞的组合等。同时，通过对比实验组和对照组体外和血液中多种细胞因子、生长因子和免疫细胞的变化来揭示其抗炎和组织修复的作用机制。此研究所揭示的新的细胞因子及信号传导途径将作为进一步筛选大分子和小分子治疗骨性关节炎的基础。本研究成果将从源头上拓展骨性关节炎的细胞学和分子学治疗手段。

中文关键词： 骨关节炎；人脐带间充质干细胞

英文摘要： Osteoarthritis is one of the most common clinical diseases, however, without effective treatment methods in the current clinical practice. Our goal is to develop stem cell interventions at the early or mid stages of osteoarthritis to repair the damaged cartilage while reducing the recipients' inflammatory responses. Our previous studies have demonstrated that human cord blood derived Unrestricted Somatic Stem Cells (USSC) facilitates wound healing through multiple mechanisms including release of trophic factors, cell replacement and immune modulations, in both animal models of wounding and inherited skin disease. USSCs have also demonstrated the ability to different into cartilage in vitro. Currently, GMP-grade USSCs have been produced by our collaborators, ensuring their immediate clinical applications. Here we propose to investigate the efficacy of USSCs in the treatment of osteoarthritis using our successfully established rabbit model. We will further establish the best treatment conditions, i.e., in vitro modulation, implantation timing, methods and routes, and combinations of different implanting cell populations. Meanwhile, we will investigate the cellular mechanisms for the anti-inflammatory and regenerative roles of USSCs, by comparing the multitudes of cytokines, growth factors and immune cell changes in experimental and control groups using in vitro and in vivo approaches. Novel growth factors and signaling transduction pathways implicated in the study will then be the basis for our screening for novel factors and small molecules in the treatment of osteoarthritis. In summary, our proposed study will provide fundamental treatment options, utilizing cutting edge stem cell therapy and potential macromolecule/small molecule interventions, for osteoarthritis.

英文关键词： Cold blood stem cell;Osteoarthritis;USSC