骨髓间充质干细胞源性微囊泡治疗软骨损伤的机制研究

软骨损伤是临床常见的由创伤或活动过度导致的关节疾病，目前没有满意的治疗方法。间充质干细胞（MSCs）曾是软骨损伤修复领域中的研究热点，但随研究深入，其免疫调节的双重性及恶性转化的可能性限制了其进一步应用。最新研究表明，MSCs源性微囊泡（MSCs-MVs）不但同样具有损伤组织的再生修复作用，并且可抑制自身反应性淋巴细胞增殖、抑制恶性转化，因而较MSCs更具安全性和优越性。课题组经多个文献系统检索，目前未发现MSCs-MVs在软骨组织损伤修复方面的研究报道。课题组拟体外培养新西兰白兔骨髓MSCs，分离提取BMSCs-MVs，通过体外和体内实验，从软骨细胞、软骨细胞信号转导通路、软骨组织三个层面观察其对软骨细胞的生物活性影响，探索其在软骨细胞间的信号转导机制，评价其对软骨损伤的治疗效果，进行BMSCs-MVs在软骨损伤修复过程中的现象研究和机制研究，为软骨损伤修复领域提供新的思路和实验基础。

Cartilage injury is a commmon disease nowdays caused by trauma or hyperactivity,which can cause osteoarthritis eventually without effective treatments. Unfortunately, there is no efficient therapy for cartilage injury so far. MSCs was the research focus on cartilage injury repairing, however, the defects such as the possibility of malignant transformation were gradually exposed and thereby limited further application of MSCs. According to the recent research, MSCs-MVs(microvesicles) has more advantages than MSCs. MSCs-MVs not only has the function of tissue repairing and regenerating, but can inhibit tissue malignant transformation. Although these exciting results, interestingly, there is no research untill now about cartilage injury repairing with MSCs-MVs. Therefore, we plan to isolate MVs from bone marrow stem cells(BMSCs) of New Zealand rabbits, and inject BMSCs-MVs into the knee articular cavum which has been prepared models with NWZ rabbits. The purpose of this research is to interpret the effects of BMSCs-MVs on chondrocytes and cartilage tissue through the study in vivo and ex vivo, and analyze the signaling pathways through which BMSCs-MVs act on chondrocytes ,and try to explain the mechanisms of cartilage injury repairing. The study will be anticipated to find an more efficient and safer treatment to cartilage injury.