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Protective effects of mesenchymal stem cells overexpressing extracellular regulating kinase 1/2 against stroke in rats

Gao, X.ORCID: 0000-0003-2491-8169, Wu, D., Dou, L., Zhang, H., Huang, L., Zeng, J., Zhang, Y., Yang, C., Li, H., Liu, L., Ma, B. and Yuan, Q. (2019) Protective effects of mesenchymal stem cells overexpressing extracellular regulating kinase 1/2 against stroke in rats. Brain Research Bulletin, 149 . pp. 42-52.

Link to Published Version: https://doi.org/10.1016/j.brainresbull.2019.04.006
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Abstract

Objective
Although transplantation of bone marrow-derived mesenchymal stem cells (MSCs) has shown beneficial effects on stroke, lower survival of MSCs limits effects. Extracellular regulating kinase 1/2 signaling (ERK1/2) is crucial for cell survival, differentiation, and proliferation. This study was designed to explore whether MSCs modified by over-expressing ERK1/2 may reinforce beneficial effects on stroke in rats.

Methods
rat MSCs transfected with ERK1/2 and empty lentivirus to generate MSCs overexpressing ERK1/2 (ERK/MSCs) and MSCs (as a control), respectively. In vitro, ERK/MSCs were plated and exposed to glutamate-induced condition, and viability of ERK/MSCs was measured. Furthermore, neural induction of ERK/MSCs was investigated in vitro. Cerebral ischemic rats were induced by occluding middle cerebral artery, and then were stereotaxically injected into ipsilateral right lateral ventricle with ERK/MSCs or MSCs 3 days after stroke and survived for 7 or 14 days after injection.

Results
ERK/MSCs showed better viability in physiological and glutamate-induced neurotoxic conditions compared to MSCs. After neural induction, more neurons were be differentiated from ERK/MSCs than from MSCs. After transplantation, more numbers of grafted cells and improved functional recovery were observed in ERK/MSCs-treated rats compared with MSCs-treated rats. Compared with MSCs treatment, ERK/MSCs treatment significantly increased proliferation of neural stem cells in the subventricle zone (SVZ) and the MAP2/nestin double-labeled cells adjacent to the SVZ, enhanced the numbers of reactive astrocytes while suppressed microglial activation. Besides, TNF-α level was elevated in ERK/MSCs-treated rats. Conclusion:ERK/MSCs transplantation showed better functional recovery after stroke in rats, likely in part through enhancing survival of MSCs and possibly by modulating the proliferation, neuronal de-differentiation and neuroinflammation.

Item Type: Journal Article
Publisher: Elsevier Inc.
Copyright: © 2019 Elsevier Inc.
URI: http://researchrepository.murdoch.edu.au/id/eprint/49511
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