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Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation

Journal of Zhejiang University SCIENCE B volume 13, pages 616–623 (2012)Cite this article

Abstract

Objective

Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation.

Methods

MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson’s trichrome staining, respectively.

Results

Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group.

Conclusions

Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.

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Affiliations

  1. Cardiovascular Key Lab of Zhejiang Province, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China

    Xian-bao Liu, Han Chen, Hui-qiang Chen, Xin-yang Hu, Ya-ping Wang, Zhi Jiang, Yin-chuan Xu, Mei-xiang Xiang & Jian-an Wang

  2. Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China

    Xian-bao Liu, Han Chen, Hui-qiang Chen, Xin-yang Hu, Ya-ping Wang, Zhi Jiang, Yin-chuan Xu, Mei-xiang Xiang & Jian-an Wang

  3. Department of Intensive Care Unit, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, 310006, China

    Mei-fei Zhu

Authors
  1. Xian-bao Liu
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  2. Han Chen
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  3. Hui-qiang Chen
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  7. Zhi Jiang
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  9. Mei-xiang Xiang
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  10. Jian-an Wang
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Corresponding author

Correspondence to Jian-an Wang.

Additional information

The two authors contributed equally to this work

Project supported by the Natural Science Foundation of Zhejiang Province (No. Y2100362) and the Qianjiang Talents Project of Science and Technology Department of Zhejiang Province (No. 2011R10022), China

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Liu, Xb., Chen, H., Chen, Hq. et al. Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation. J. Zhejiang Univ. Sci. B 13, 616–623 (2012). https://doi.org/10.1631/jzus.B1201004

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  • DOI: https://doi.org/10.1631/jzus.B1201004

Key words

  • Mesenchymal stem cells
  • Angiopoietin-1
  • Preconditioning
  • Survival
  • Myocardial infarction

CLC number

  • R541.4