Effects of Extracellular Vesicles from Mesenchymal Stem Cells on Oxygen-glucose Deprivation/reperfusion-induced Neuronal Injury

Overview

Journal World J Emerg Med

Specialty Emergency Medicine

Date 2021 Jan 28

PMID 33505552

Citations 4

Authors

Shuang-Shuang Gu

Xiu-Wen Kang

Jun Wang

Xiao-Fang Guo

Hao Sun

Lei Jiang

Jin-Song Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Small extracellular vesicles (sEVs) from bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential for cerebral ischemic diseases. However, the mechanisms by which BMSC-derived sEVs (BMSC-sEVs) protect neurons against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we explored the neuroprotective effects of BMSC-sEVs in the primary culture of rat cortical neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) injury.

Methods: The primary cortical neuron OGD/R model was established to simulate the process of cerebral I/R . Based on this model, we examined whether the mechanism through which BMSC-sEVs could rescue OGD/R-induced neuronal injury.

Results: BMSC-sEVs (20 μg/mL, 40 μg/mL) significantly decreased the reactive oxygen species (ROS) productions, and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Additionally, BMSC-sEVs prevented OGD/R-induced neuronal apoptosis , as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) leakage, decreased terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining-positive cells, down-regulated cleaved caspase-3, and up-regulated Bcl-2/Bax ratio. Furthermore, Western blot and flow cytometry analysis indicated that BMSC-sEV treatment decreased the expression of phosphorylated calcium/calmodulin-dependent kinase II (p-CaMK II)/CaMK II, suppressed the increase of intracellular calcium concentration ([Ca]) caused by OGD/R in neurons.

Conclusions: These results demonstrate that BMSC-sEVs have significant neuroprotective effects against OGD/R-induced cell injury by suppressing oxidative stress and apoptosis, and Ca/CaMK II signaling pathways may be involved in this process.

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