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Brain Res. 2019 Sep 3;1725:146432. doi: 10.1016/j.brainres.2019.146432. [Epub ahead of print]

Hypoxia conditioning enhances neuroprotective effects of aged human bone marrow mesenchymal stem cell-derived conditioned medium against cerebral ischemia in vitro.

Author information

1
Department of Neurobiology, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
2
Department of Neurobiology, Capital Medical University, Beijing 100069, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
3
Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
4
Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
5
Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA.
6
Beijing Key Laboratory of Hypoxia Conditioning Translational Medicine, Beijing 100053, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China; Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn.

Abstract

Therapeutic transplantation of autologous bone marrow mesenchymal stem cells (BMSCs) holds great promise for ischemic stroke, yet the efficacy is negatively impacted by aging. Here, we examined whether hypoxia conditioning could enhance aged human BMSCs-induced neuroprotection via secretome action. Primary cultured mouse neurons were exposed to oxygen glucose deprivation (OGD) to mimic ischemic stroke in vitro, then randomized into a hypoxia conditioned aged human BMSCs-conditioned medium (BMSC-hypoCM) versus normoxia conditioned (BMSC-norCM). After 22 h of reperfusion, cell viability was significantly increased in neurons treated with BMSC-hypoCM rather than BMSC-norCM. ELISA revealed that hypoxia conditioning enhanced vascular endothelial growth factor (VEGF) release into BMSC-derived CM. Blocking the VEGF receptor negated BMSC-hypoCM-induced protection for neurons against OGD insult. Altogether, our data indicates that hypoxia conditioning improves aged human BMSCs' therapeutic efficacy for neurons with ischemic challenge, in part via promoting secretion of VEGF.

KEYWORDS:

Aging; Bone marrow mesenchymal stem cells (BMSCs); Conditioned medium (CM); Hypoxia; Neuroprotection

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