Human endometrial stem cells confer enhanced myocardial salvage and regeneration by paracrine mechanisms

Authors

  • Zhi Jiang,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Xinyang Hu,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
    2. Key lab of cardiovascular disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Hong Yu,

    1. Key lab of cardiovascular disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Yinchuan Xu,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Lihan Wang,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Han Chen,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Huiqiang Chen,

    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Rongrong Wu,

    1. Key lab of cardiovascular disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Zhaocai Zhang,

    1. Key lab of cardiovascular disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Chunsheng Xiang,

    1. Zhejiang-California International NanoSystems Institute, Zhejiang University, Hangzhou, China
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  • Keith A Webster,

    1. Vascular Biology Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
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  • Jian-an Wang

    Corresponding author
    1. Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
    2. Key lab of cardiovascular disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
    • Correspondence to: Jian-An WANG, M.D., Ph.D., Department of Cardiology, Key Lab of Cardiovascular Disease, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

      Tel.: 086-571-87315001

      Fax: 086-571-87037885

      E-mail: jian_an_wang@yahoo.com

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Abstract

Human endometrial stem cells (EnSCs) have the potential to be ‘off the shelf’ clinical reagents for the treatment of heart failure. Here, using an immunocompetent rat model of myocardial infarction (MI), we provide evidence that the functional benefits of EnSC transplantation are principally and possibly exclusively through a paracrine effect. Human EnSCs were delivered by intramyocardial injection into rats 30 min. after coronary ligation. EnSC therapy significantly preserved viable myocardium in the infarct zone and improved cardiac function at 28 days. Despite increased viable myocardium and vascular density, there was scant evidence of differentiation of EnSCs into any cardiovascular cell type. Cultured human EnSCs expressed a distinctive profile of cytokines that enhanced the survival, proliferation and function of endothelial cells in vitro. When injected into the peri-infarct zone, human EnSCs activated AKT, ERK1/2 and STAT3 and inhibited the p38 signalling pathway. EnSC therapy decreased apoptosis and promoted cell proliferation and c-kit+ cell recruitment in vivo. Myocardial protection and enhanced post-infarction regeneration by EnSCs is mediated primarily by paracrine effects conferred by secreted cytokines that activate survival pathways and recruit endogenous progenitor stem cells. Menstrual blood provides a potentially limitless source of biologically competent ‘off the shelf’ EnSCs for allogeneic myocardial regenerative medicine.

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