肺源性微囊泡诱导移植间充质干细胞定向分化治疗肺纤维化

项目名称： 肺源性微囊泡诱导移植间充质干细胞定向分化治疗肺纤维化

项目编号： No.81500053

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡若愚

作者单位： 东南大学

项目金额： 18万元

中文摘要： 肺泡上皮细胞(AEC)死亡、细胞间连接结构破坏是肺纤维化(PF)发生的始动环节。早期高效地修复受损及死亡的AEC，重建其连接的完整性是治疗PF的有效途径。我们的研究证明：通过肺内移植MSC进而分化为AEC以填补死亡细胞龛位能有效地抑制PF的进展。然而，移植MSC向AEC分化的效率极低。此为有效利用MSC进行肺组织再生修复的瓶颈问题。微囊泡(MV)内含核酸、蛋白等信息物质，是细胞间信息传递的重要途径。受损细胞通过释放MV将自身信息传递给干细胞，诱导其向受损细胞类型分化以参与组织重建。本研究将通过肺源性MV(LDMV)与MSC共培养，体外证实LDMV对MSC向AEC分化的促进作用；并将经LDMV预处理的MSC用于PF模型大鼠的肺内移植治疗，使移植的MSC在肺内更多地向AEC分化，更好地参与受损肺组织的早期修复，提高治疗效率。本研究将为利用干细胞组织再生特性治疗PF提供实验依据及理论支持。

中文关键词： 肺纤维化；间充质干细胞；微囊泡；肺泡上皮细胞；定向分化

英文摘要： The death of alveolar epithelial cells (AECs) and the destruction of the cell junctions are considered as initial factors of the pulmonary fibrosis (PF). Thus, the effectively repair of the destroyed and the dead AECs which result in the rebuilt of the cell junction integrity at the early stage should be a feasible way to prevent the PF process. Our previous investigations have proved that mesenchymal stem cells (MSCs) can differentiate into AECs. And we can suppress the proceeding of the PF by MSCs engraftment and inducing them differentiating into AECs which may fill the niches of the dead AECs. However, the proportion of the MSCs differentiated into AECs was extremely low. A dramatic enhancement of the AECs differentiation proportion of MSCs exists as a bottleneck problem. Microvesicles (MVs), which contain nucleic acids and proteins , are an important way of cell-to-cell communication. Injured cells can send messages to stem cells through MVs delivery and induce the recipient stem cells differentiating into the same phenotype and migrating to the injured tissues to repair later on. Our in vitro study will aim on the differentiation proportion enhancement of MSCs by co-culture with the lung derived microvesicles (LDMVs). And in vivo study will try to significantly alleviate PF of the SD rat model by MSCs lung engraftment which are pretreated with LDMVs in hope that more MSCs can differentiate into AECs to exert their healing effects. The results of our research may not only be important in revealing the mechanisms of PF but also provide substantial experimental references of PF treatment through regeneration properties of stem cells .

英文关键词： pulmonary fibrosis;mesenchymal stem cells;microvesicles;alveolar epithelial cells;directional differentiation