Objectives: 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.Methods: 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.Results: 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.Conclusion: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

No abstract

Microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) and miR-21 were demonstrated to ameliorate renal ischemia-reperfusion injury (IRI). Since hUC-MSC-MVs contained a substantial quantity of miR-21, we speculated that miR-21 might account for a part of the therapeutic effects of hUC-MSCs-MVs. The human tubule epithelial (HK-2) cells were cultured under low oxygen (LO) condition to mimic a cellular IRI model. A rat model of unilateral renal IRI was established. A co-culture model of HK-2 cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs in HK-2 cell apoptosis and mechanism. The results showed that hUC-MSCs-MVs inhibited LO-induced HK-2 cell apoptosis through transferring miR-21 to HK-2 cells. Mechanistically, miR-21 directly targeted and negatively regulated programmed cell death protein 4 (PDCD4) in HK-2 cells. Moreover, PDCD4 overexpression in HK-2 cells abrogated the hUC-MSCs-MVs-inhibited HK-2 cell apoptosis under LO condition. Additionally, the beneficial effect of MSC-MVs on rat renal IRI was partly eliminated when miR-21 was knocked down in MSCs. Taken together, MSC-MVs inhibit tubular epithelial cell apoptosis and ameliorate renal IRI, at least partially, via delivery of miR-21.