BMP-7过表达的骨髓间充质干细胞对矽肺的拮抗作用及相关机制研究

项目名称： BMP-7过表达的骨髓间充质干细胞对矽肺的拮抗作用及相关机制研究

项目编号： No.81472958

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： 田琳

作者单位： 首都医科大学

项目金额： 70万元

中文摘要： 矽肺是我国发病最多、对劳动者健康危害最严重的职业病，尚无有效的治疗方法。研究显示骨髓间质干细胞（BMSCs）是最具应用前景的细胞与基因治疗的理想靶细胞。课题组前期研究发现骨形态发生蛋白-7（BMP-7）具有明显的拮抗矽肺纤维化作用。本项目利用Micro CT 活体肺组织扫描、小动物活体成像系统、Transwell共培养体系、双光子显微镜、抗体芯片等技术，通过动态染尘的方式制备大鼠矽肺模型，观察BMP-7过表达BMSCs（BMP-7-BMSCs）干预对大鼠肺纤维化的抑制作用；建立体外非接触无损伤大鼠肺组织和矽肺组大鼠肺组织共培养模型，观察BMSCs的分泌功能及向肺泡上皮细胞分化情况。系统研究BMP-7过表达BMSCs在体内的植入和分化、输入时间窗、旁分泌效应，探讨BMP-7过表达BMSCs移植对石英致大鼠肺纤维化的保护机制。该研究为进一步探索防治矽肺的有效途径，提高患者生活质量提供新的思路。

中文关键词： 肺纤维化；骨髓间充质干细胞；骨形态发生蛋白-7；矽肺

英文摘要： Silicosis is the most serious occupational disease for laborers,which has the highest incidence rates, and there is no effective treatment now.Bone marrow mesenchymal stem cells (BMSCs), as an ideal target for cell- and gene-therapy, have most possible application foreground. Previous studies published by our research group have found that bone morphogenetic protein-7 (BMP-7) had effective antagonistic effect on silicosis fibrosis. In this research, technologies including Transwell co-culture system, Micro CT for lung tissue scanning in vivo, small animal in vivo imaging system, two-photon microscopy and antibody chip technology are used, and the silicosis model is established through dynamic dust exposure in rats in order to investigate the inhibitory effect of BMP-7 gene overexpression BMSCs (BMP-7-BMSCs) intervention on rats fibrosis. In vitro, the lung tissues co-culture systems in both normal with no injury and silicosis groups are set to induce the differentiation of BMSCs to alveolar epithelial cells. Furthermore, the implantation and differentiation, input time window, paracrine effects of BMP-7-BMSCs in vivo are systemically studied to explore the protective mechanisms of BMP-7-BMSCs transplantation on quartz-induced fibrosis. The research would provide innovative way for the further exploration of effective strategieson silicosis treatment and improvement of patients' life quality.

英文关键词： pulmonary fibrosis;bone marrow mesenchymal stem cell;bone morphogenetic protein-7;silicosis