Hypoxic preconditioning attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells1

Authors

  • Jian-an WANG,

    Corresponding author
    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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    • 5

      These two authors contributed equally to the study.

  • Tie-long CHEN,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
    2. Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, China
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    • 5

      These two authors contributed equally to the study.

  • Jun JIANG,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Heng SHI,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Chun GUI,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Rong-hua LUO,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Xiao-jie XIE,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Mei-xiang XIANG,

    1. Department of Cardiology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • Xing ZHANG

    1. Clinical Research Institute, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
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  • 1

    This work was partly supported by grants from the National Natural Science Foundation of China (No 30670868) and a grant from the Zhejiang province Natural Science Foundation (No R206007).

Correspondence to Prof Jian-an WANG. Phn 86-138-0578-6328. Fax 86-571-8778-3688. E-mail wang_jian_an@tom.com

Abstract

Aim: 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-α, 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. Conclusion: 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.

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