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However, the harsh microenvironment induced by cerebral ischemia\/reperfusion restricts the survival rate and therapeutic efficiency of the engrafted UC-MSCs. In this study, we explored whether small extracellular vesicles (EVs) derived from injured neuronal cells following exposure to cerebral ischemia\/reperfusion insult affect the survival of transplanted UC-MSCs. To establish a simulation of cerebral ischemia\/reperfusion microenvironment comprising engrafted UC-MSCs and neuronal cells, we cocultured EVs derived from injured N2A cells, caused by exposure to oxygen-glucose deprivation and reperfusion (OGD\/R) insult, with UC-MSCs in a conditioned medium. Coculture of UC-MSCs with EVs exacerbated the OGD\/R-induced apoptosis and oxidative stress. Suppression of EVs-release via knock-down of Rab27a effectively protected the UC-MSCs from OGD\/R-induced insult. Moreover, hypoxia preconditioning not only elevated the survival of UC-MSCs but also improved the paracrine mechanism of injured N2A cells. Altogether, these results show that EVs from injured N2A cells exacerbates OGD\/R-induced injury on transplanted UC-MSCs <jats:italic>in vitro<\/jats:italic>. Hypoxia preconditioning enhances the survival of the engrafted-UC-MSCs; hence, thus could be an effective approach for improving UC-MSCs therapy in ischemic stroke.<\/jats:p>","DOI":"10.1155\/2020\/9768713","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T23:34:14Z","timestamp":1595028854000},"page":"1-26","source":"Crossref","is-referenced-by-count":21,"title":["Effects of the Insulted Neuronal Cells-Derived Extracellular Vesicles on the Survival of Umbilical Cord-Derived Mesenchymal Stem Cells following Cerebral Ischemia\/Reperfusion Injury"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7453-676X","authenticated-orcid":true,"given":"Yan","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China"},{"name":"Department of Neurosurgery, 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