间充质干细胞来源微泡（MSC-MVs）具有促血管生成的作用，其包含的miRNA可能是发挥作用的重要媒介。预初实验发现与肿瘤血管新生密切相关的miR-21在MSC-MVs中表达，由此我们推测MSC-MVs可能通过miR-21作用于血管内皮细胞，通过下调PTEN表达而抑制PIP3的去磷酸化，进而激活 AKT信号通路等系列变化，促进血管内皮细胞增殖、迁移和血管生成。本研究将通过miRNA抑制剂阻断内源性miR-21的功能，在体外细胞水平和体内下肢缺血模型中验证miR-21的促血管作用，并监测其下游信号通路分子的表达变化，阐明其调控的分子机制；在此基础上进一步通过转基因操作使MSC或人脐静脉细胞株过表达miR-21，提取细胞释放的MVs，在细胞和动物模型中验证经基因改造的MVs的有效性、安全性及时限性。该研究的成功有望突破现有干细胞移植治疗理念，为创伤修复和组织再生提供新的治疗模式。

Mesenchymal stem cell-derived MVs (MSC-MVs) possess potent proangiogenic potential. The major component miRNAs may play an important role in the proangiogenic process. In the preliminary study, we found that miR-21, which is critical for tumor angiogenesis, was detected in MSC-MVs by gene chip analysis. Therefore, we propose that MSC-MVs promote endothelial cell proliferation, migration and vessel formation through miR-21, which down-regulate PTEN, inhibit the dephosphorylation of PIP3, and subsequently activate AKT pathway. In the current study, we will inhibit the miR-21 function by miRNA antagomir to verify the proangiogenic role of miR-21 in cultured cells and a limb-ischemic model. The related down-stream signaling pathway molecules will be monitored to reveal the detail mechanism of MSC-MVs induced angiogenesis. Moreover, miR-21 will be overexpressed in MSC by genetic manipulation, and the proangiogenic potential of MVs derived from those cells will be evaluated in vitro and in vivo. Possibly, this work will provide new evidence to support the clinical application of MSC-MVs. It will also provide an alternative strategy in the stem cell based tissue repair and regeneration.