Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen-glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.

Bao H ，Mao S ，Hu X ，Li L ，Tao H ，Zhou J ，Xu L ，Fang Y ，Zhang Y ，Chu L ... -  《Scientific Reports》

Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway.

Hou K ，Li G ，Zhao J ，Xu B ，Zhang Y ，Yu J ，Xu K ... -  《Journal of Neuroinflammation》

Exosomes of bone-marrow stromal cells inhibit cardiomyocyte apoptosis under ischemic and hypoxic conditions via miR-486-5p targeting the PTEN/PI3K/AKT signaling pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a major obstacle in the treatment of ischemic heart disease. Recent studies have shown that exosomes-small membrane vesicles secreted by most cell types-could have a protective effect on the ischemic myocardium. In this study we explored the effect of exosomes derived from bone-marrow stromal cells (BMSC-exo) on cardiomyocyte apoptosis and MIRI. Exosomes were purified from culture media using the ExoQuick kit and observed using transmission electron microscopy. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell apoptosis was analyzed by flow cytometry using the Annexin-V/PI stain. The expression levels of microRNA (miRNA), messenger RNA (mRNA) and PTEN/PI3K/AKT-pathway-related proteins were detected by qRT-PCR and western blot, respectively. Myocardial ischemia was simulated by incubating H9C2 cells in a hypoxia/reoxygenation (H/R) conditioned rat MIRI model. BMSC-exo induced the proliferation of H9C2 cells and rescued H9C2 cells from apoptosis in the H/R model, indicating that BMSC-exo has a protective effect on cardiomyocyte injury caused by H/R. Using transgenic H9C2 cells, we found that miR-486-5p in BMSC-exo suppressed the H/R-triggered apoptosis of H9C2 cells. In addition, BMSC-exo repressed the expression of PTEN in H9C2 cells via miR-486-5p, and subsequently activated the PI3K/AKT pathway in vitro. Moreover, the myocardial injury caused by ischemia/reperfusion was repaired by BMSC-exo which activates the PI3K/AKT pathway via miR-486-5p in vivo. Our results suggested that exosomes from BMSCs have a protective effect on myocardium ischemic injury. MiR-486-5p carried by BMSC-exo plays a pivotal role in the regulatory process by suppressing PTEN expression, activating the PI3K/AKT signaling pathway, and subsequently inhibiting the apoptosis of injured cardiomyocytes.

Sun XH ，Wang X ，Zhang Y ，Hui J ... -  《-》

Glioma stem cells-derived exosomal miR-26a promotes angiogenesis of microvessel endothelial cells in glioma.

Wang ZF ，Liao F ，Wu H ，Dai J ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Exosomes Derived from BMSCs Ameliorate Intestinal Ischemia-Reperfusion Injury by Regulating miR-144-3p-Mediated Oxidative Stress.

Intestinal ischemia-reperfusion (I/R) injury is a critical pathophysiological process involved in many acute and critical diseases, and it may seriously threaten the lives of patients. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) may be an effective therapeutic approach for I/R injury. This study aimed to investigate the role and possible mechanism of BMSC-exos in intestinal I/R injury in vivo and in vitro based on the miR-144-3p and PTEN/Akt/Nrf2 pathways. BMSC-exos were isolated from mouse BMSCs by super centrifugation methods. The effects of BMSC-exos on I/R intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway were explored in vivo and in vitro. Furthermore, the relationship between miR-144-3p and PTEN was confirmed by a dual-luciferase reporter assay. The miR-144-3p mimic and inhibitor were used to further clarify the role of miR-144-3p in the mitigation of intestinal I/R by BMSC-exos. BMSC-exos effectively alleviated intestinal pathological injury, reduced intestinal cell apoptosis, relieved oxidative stress and regulated the PTEN/Akt/Nrf2 pathway in vivo and in vitro. In addition, miR-144-3p was significantly reduced in the oxygen and glucose deprivation/reperfusion cell model, and miR-144-3p could directly target PTEN to regulate its expression. Additional studies showed that changing the expression of miR-144-3p in BMSC-exos significantly affected the regulation of intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway in I/R, suggesting that miR-144-3p in BMSC-exos plays an important role in regulating the PTEN/Akt/Nrf2 during intestinal I/R. BMSC-exos carrying miR-144-3p alleviated intestinal I/R injury by regulating oxidative stress.

Zhang G ，Wan Z ，Liu Z ，Liu D ，Zhao Z ，Leng Y ... -  《-》