我们前期研究在间充质干细胞(MSC)来源的微泡(MV)中检出包括miR-200家族等276种miRNA，并发现MV具有肾损伤修复作用。既往研究显示促红细胞生成素(EPO)可在纠正肾性贫血的同时减轻肾损伤，并增加MSC的活力。本项目将MSC和MV研究新进展，与基因治疗载体的领先技术相结合，探索突变型双链腺相关病毒(scAAV)介导EPO基因修饰MSC来源的MV(EPO-MV)治疗慢性肾衰竭(CRF)的新方法。本研究将：⑴深入探讨MV的肾修复作用；⑵明确EPO-MV是否进一步促进肾损伤修复；⑶探明MV和EPO-MV依赖传递miRNA如miR-200和miR-29家族而发挥肾修复作用及其机制。MV治疗有望成为干细胞治疗的新方向，而基因修饰MSC来源的MV，这一特定设计的"超微泡"可能成为细胞治疗新的方法。本研究预期在CRF的治疗上有所突破，为CRF干细胞治疗提供新途径。

In our previous study, more than 276 kinds of miRNA, including miR200 and miR29 families, have been detected in the microvesicles (MV) derived from mesenchymal stem cells (MSC). And we have found that MV released from MSC may account for mitigating injury or favouring repair in the impaired kidney. Additionally several observations have demonstrated that erythropoietin (EPO) could ameliorate renal anemia and renal injury, as well as enhance the vitality of MSC. Therefore, the present project aims to explore the role of MV derived from MSC modified with EPO gene by novel self-complementary AAV (EPO-MSC-MV) in the treatment of chronic renal failure (CRF). The study follows the latest progress in the field of MSC and MV therapy and the international forefront of gene therapy in the area of AAV vectors. This study will focus on: (1) exploring the function of MSC-MV in the renal restoration of chronic kidney injury; (2) determining whether EPO-MSC-MV could repair renal injury better than MSC-MV; (3) investigating the possible renal repair functions and mechanisms associated with miRNA transferred by MSC-MV or EPO-MSC-MV, such as miR-200 and miR-29 families. The administration of MV may provide a promising opportunity for stem cell therapeutic research. MV derived from genetically-modified MSC, the custom-engineered super-micro-vesicles, may become a new class of cell-derived therapeutics. The project is expected to achieve a breakthrough in stem cell therapy for CRF.