• Open Access

Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction

Authors

  • Haibin Wang,

    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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  • Zhiqiang Liu,

    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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  • Dexue Li,

    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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  • Xuan Guo,

    1. Department of Chemical and Biomolecular Engineering, Rice University, MS-362, Houston, TX, USA
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  • F. Kurtis Kasper,

    1. Department of Bioengineering, Rice University, MS-142, Houston, TX, USA
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  • Cuimi Duan,

    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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  • Jin Zhou,

    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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  • Antonios G. Mikos,

    Corresponding author
    1. Department of Bioengineering, Rice University, MS-142, Houston, TX, USA
    2. Department of Chemical and Biomolecular Engineering, Rice University, MS-362, Houston, TX, USA
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  • Changyong Wang

    Corresponding author
    1. Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China
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Changyong WANG, M.D., Ph.D., Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China. Tel.: +86-10-66931592 Fax: +86-10-68166874 E-mail: wcy2000@yahoo.com

Antonios G. MIKOS, Ph.D., Departments of Bioengineering and Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA. Tel.: +1-713-348-5355 Fax: +1-713-348-4244 E-mail: mikos@rice.edu

Abstract

In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation.

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