Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells.
OBJECTIVE
Mesenchymal stem cells (MSC) are a promising candidate for cardiac replacement therapies. However, the majority of transplanted MSC are readily lost after transplantation because of poor blood supply, ischemia-reperfusion, and inflammatory factors. We aimed to study the effects of hypoxia preconditioning (HPC) on hypoxia/reoxygenation-induced apoptosis of MSC.


METHODS
Three generations of MSC were divided into 6 groups, including the normal group, hypoxia-reoxygenation (H/R) group, cyclosporine A (CsA), and the HPC 10 min, 20 min, and 30 min groups. The apoptotic index, cell viability, mitochondrial membrane potential, translocation of Bcl-2 and bax, extracellular regulated kinase (ERK), Akt, hypoxia-inducible factor 1-alpha, and the vascular endothelial growth factor (VEGF) were tested after H/R treatment.


RESULTS
HPC decreased the apoptotic index and increased the viability induced by H/R. Moreover, HPC markedly stabilized mitochondrial membrane potential, upregulated Bcl-2 and VEGF expressions, and increased the phosphorylation of ERK and Akt. As a positive control, CsA has the same function as HPC, except for promoting ERK and Akt phosphorylation and upregulating VEGF.


CONCLUSIONS
HPC had a protective effect against MSC apoptosis induced by H/R via stabilizing mitochondrial membrane potential, upregulating Bcl-2 and VEGF, and promoting ERK and Akt phosphorylation. HPC has implications for the development of novel stem cell protective strategies.
Wang
Jian-an
JA
Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. wang_jian_an@tom.com
Chen
Tie-long
TL
Jiang
Jun
J
Shi
Heng
H
Gui
Chun
C
Luo
Rong-hua
RH
Xie
Xiao-jie
XJ
Xiang
Mei-xiang
MX
Zhang
Xing
X
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley