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

Ying Zhang; Longhui Ma; Yuwen Su; Li Su; Xiaoxi Lan; Di Wu; Song Han; Junfa Li; Lauren Kvederis; Sydney Corey; Cesar V Borlongan; Xunming Ji

doi:10.1016/j.brainres.2019.146432

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

Brain Res. 2019 Dec 15:1725:146432. doi: 10.1016/j.brainres.2019.146432. Epub 2019 Sep 3.

Authors

Ying Zhang¹, Longhui Ma², Yuwen Su², Li Su³, Xiaoxi Lan³, Di Wu⁴, Song Han², Junfa Li², Lauren Kvederis⁵, Sydney Corey⁵, Cesar V Borlongan⁵, Xunming Ji⁶

Affiliations

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.

PMID: 31491422
DOI: 10.1016/j.brainres.2019.146432

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aged
Animals
Brain Ischemia / metabolism*
Cell Hypoxia
Cell Survival
Culture Media, Conditioned
Disease Models, Animal
Humans
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism*
Neurons / metabolism*
Primary Cell Culture
Vascular Endothelial Growth Factor A / metabolism

Substances

Culture Media, Conditioned
Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, mouse