Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke

BackgroundSmall extracellular vesicles (sEV) secreted by mesenchymal stem cells (MSC) derived from human induced pluripotent stem cells (iPSC, iMSC-sEV) are considered to have great potential in treating ischemic diseases. Angiogenesis play an important role in post-stroke recovery. However, no stud...

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Veröffentlicht in:Stem cell research & therapy 2020-07, Vol.11 (1), p.1-313, Article 313
Hauptverfasser: Xia, Yuguo, Ling, Xiaozheng, Hu, Guowen, Zhu, Qingwei, Zhang, Juntao, Li, Qing, Zhao, Bizeng, Wang, Yang, Deng, Zhifeng
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Sprache:eng
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Zusammenfassung:BackgroundSmall extracellular vesicles (sEV) secreted by mesenchymal stem cells (MSC) derived from human induced pluripotent stem cells (iPSC, iMSC-sEV) are considered to have great potential in treating ischemic diseases. Angiogenesis play an important role in post-stroke recovery. However, no studies have yet been conducted to systemically examine the effect and the underlying mechanism of iMSC-sEV on angiogenesis under brain ischemia conditions.MethodsIschemic stroke model was performed in rats induced by middle cerebral artery occlusion (MCAO), and the pro-angiogenic capacity of iMSC-sEV was measured. The in vitro effects of iMSC-sEV on the migration and tube formation of endothelial cells were investigated, respectively. Autophagy and autophagy-related signaling pathway were detected in vivo and in vitro.ResultsWe found that iMSC-sEV significantly reduced infarct volume, enhanced angiogenesis, and alleviated long-term neurological deficits in rats after stroke. We also demonstrated that iMSC-sEV increased migration and tube formation of endothelial cells in vitro. A further mechanism study revealed that the pro-angiogenic effect of iMSC-sEV was correlated with a reduction in autophagy. Furthermore, iMSC-sEV significantly activated signal transducer and activator of transcription 3 (STAT3), and suppression of STAT3 abolished iMSC-sEV-induced inhibition of autophagy and promotion of angiogenesis in vivo and in vitro.ConclusionsTaken together, our data indicate that iMSC-sEV promote angiogenesis after ischemic stroke, potentially, by inhibiting autophagy, a process that is partially dependent on STAT3 activation.
ISSN:1757-6512
1757-6512
DOI:10.1186/s13287-020-01834-0