Open AccessEffects of the Insulted Neuronal Cells-Derived Extracellular Vesicles on the Survival of Umbilical Cord-Derived Mesenchymal Stem Cells following Cerebral Ischemia/Reperfusion Injury
Author(s) -
Yan Huang,
Lei Zuo,
Fengbo Tan,
Zhiping Hu,
Ming Lu
Publication year - 2020
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2020/9768713
Subject(s) - mesenchymal stem cell , ischemia , umbilical cord , medicine , paracrine signalling , reperfusion injury , hypoxia (environmental) , stem cell , immunology , pharmacology , cancer research , microbiology and biotechnology , biology , pathology , chemistry , receptor , organic chemistry , oxygen
Umbilical cord-derived mesenchymal stem cells (UC-MSCs) engraftment is a potential therapy for cerebral ischemic stroke. 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 in vitro . 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.