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

Stem Cell Research & Therapy
Yuguo XiaZhifeng Deng

Abstract

Small 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. Ischemic 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. We 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 transd...Continue Reading

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Citations

Oct 11, 2020·International Journal of Molecular Sciences·Masahito KawaboriKiyohiro Houkin
Mar 22, 2021·Molecular Neurobiology·Nashmin FayaziRezvan Najafi
Apr 7, 2021·Pharmacology & Therapeutics·Amir AjoolabadyJun Ren
May 1, 2021·International Journal of Molecular Sciences·André Cronemberger AndradeDirk Strunk
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Guoyang ZhouLin Wang
May 14, 2021·Translational Stroke Research·Yiyang LiYonghua Zhao
May 11, 2021·Frontiers in Cellular Neuroscience·Hua ZhuXiaoxing Xiong
Jun 18, 2021·Frontiers in Neuroscience·Ranran DuanYanjie Jia
Aug 6, 2021·Stem Cells International·Jintao YuanFei Mao
Aug 28, 2021·International Journal of Molecular Sciences·Sunhong MoonYoon Kyung Choi

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
biopsy
transmission electron microscopy
Protein Assay
electrophoresis
flow cytometry

Software Mentioned

ImageJ
GraphPad Prism

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