Department of Pediatrics, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, 450000, Henan, China.
Department of Urology, Henan University People's Hospital; Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Stem Cell Res Ther. 2020 Mar 13;11(1):113. doi: 10.1186/s13287-020-01617-7.
Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs.
MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism.
MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR.
MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.
人脐带华通氏胶间充质干细胞（MSC-MVs）来源的微囊泡（MVs）已被证明能改善急性肺损伤（ALI）。我们之前发现 MSC-MV 转染的肝细胞生长因子部分参与了其治疗作用。由于 MSC-MVs 还含有大量在肺癌和损伤中起重要作用的 miR-100，我们推测 miR-100 可能同样是 MSC-MVs 治疗作用的一部分。
用 miR-100 抑制剂转染 MSC 以下调 MSC-MVs 中的 miR-100。用博来霉素（BLM）诱导大鼠 ALI 模型和大鼠 II 型肺泡上皮细胞系（L2）细胞损伤模型。利用肺泡上皮细胞和 MSC-MVs 的共培养模型来研究 MSC-MVs 的治疗作用和机制。
MSC-MV 治疗可减轻 BLM 处理的 L2 细胞中 BLM 诱导的细胞凋亡和炎症，并改善 BLM 诱导的 ALI 大鼠中 BLM 诱导的肺细胞凋亡、炎症和纤维化。当 MSC 中 miR-100 被敲低时，MSC-MVs 的有益作用部分消除。此外，MSC-MV 转导的 miR-100 通过靶向 mTOR 增强自噬来介导 MSC-MVs 在 ALI 中的治疗作用。
MSC-MVs 通过递送 miR-100 增强自噬并部分改善 ALI。
