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Research Paper|Volume 13, Issue 3|pp 4335—4356

CUEDC2 ablation enhances the efficacy of mesenchymal stem cells in ameliorating cerebral ischemia/reperfusion insult

Yan Huang1,2,3, Xia Xiao1, Han Xiao4, Zhiping Hu4, Fengbo Tan5
  • 1National Health Commission Key Laboratory of Birth Defects Research, Prevention, and Treatment, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410008, Hunan, P.R. China
  • 2Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, P.R. China
  • 3Hunan Provincial Key Laboratory of Neurorestoration, Changsha 410003, Hunan, P.R. China
  • 4Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, P.R. China
  • 5Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China
* Equal contribution
Received: August 29, 2020Accepted: November 13, 2020Published: January 20, 2021
https://doi.org/10.18632/aging.202394

Copyright: © 2021 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mesenchymal stem cell (MSC) therapy has been reported to be a promising therapeutic option for cerebral ischemia/reperfusion (I/R) insult. However, the poor survival rate of engrafted MSCs under unfavorable cerebral I/R-induced microenvironment inhibits their efficiency during clinical application. CUE domain-containing 2(CUECD2) exhibits its protective role on cardiomyocytes by mediating the antioxidant capacity. Our study explored the functional role of CUEDC2 in cerebral I/R challenge and determined whether CUECD2-modified MSCs could improve the efficacy of treatment of the insulted neurons. We also evaluated the possible mechanisms involved in cerebral I/R condition. Cerebral I/R stimulation suppressed CUEDC2 levels in brain tissues and neurons. siRNA-CUEDC2 in neurons significantly inhibited cerebral I/R-induced apoptosis and oxidative stress levels in vitro. Moreover, siRNA-CUEDC2 in the MSCs group remarkably enhanced the therapeutic efficacies in cerebral I/R-induced neuron injury and brain tissue impairment when compared to the non-genetic MSCs treatment group. At the molecular level, siRNA-CUEDC2 in MSCs markedly enhanced its antioxidant and anti-inflammatory effect in co-cultured neurons by upregulating glutathione peroxidase 1 (GPX1) expression levels while suppressing NF-kB activation. These findings provide a novel strategy for the utilization of MSCs to promote cerebral ischemic stroke outcomes.