Effects of extracellular vesicles from mesenchymal stem cells on oxygen-glucose deprivation/reperfusion-induced neuronal injury

doi:10.5847/wjem.j.1920-8642.2021.01.010

Abstract

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 in vitro. 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 in vivo, 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 ([Ca²⁺]_i) 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 Ca²⁺/CaMK II signaling pathways may be involved in this process.

Key words: Oxygen-glucose deprivation and reperfusion, Cortical neurons, Oxidative stress, Small extracellular vesicles

Shuang-shuang Gu, Xiu-wen Kang, Jun Wang, Xiao-fang Guo, Hao Sun, Lei Jiang, Jin-song Zhang. Effects of extracellular vesicles from mesenchymal stem cells on oxygen-glucose deprivation/reperfusion-induced neuronal injury[J]. World Journal of Emergency Medicine, 2021, 12(1): 61-67.

Figures/Tables 3

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