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Journal of Cellular Biochemistry

Transplantation of iPSc Ameliorates Neural Remodeling and Reduces Ventricular Arrhythmias in a Post-Infarcted Swine Model

Authors

  • Fengxiang Zhang,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Guixian Song,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Xiaorong Li,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Weijuan Gu,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Yahui Shen,

    1. Department of Cardiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China
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  • Minglong Chen,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Bing Yang,

    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
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  • Lingmei Qian,

    Corresponding author
    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
    • Correspondence to: Dr. Lingmei Qian, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.

      E-mail: lmqian@njmu.edu.cn

      Correspondence to: Kejiang Cao, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.

      E-mail: kejiangcao@163.com

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  • Kejiang Cao

    Corresponding author
    1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
    • Correspondence to: Dr. Lingmei Qian, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.

      E-mail: lmqian@njmu.edu.cn

      Correspondence to: Kejiang Cao, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China.

      E-mail: kejiangcao@163.com

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  • Fengxiang Zhang, Guixian Song, and Xiaorong Li contributed equally to this study.
  • Conflict of Interest: No conflict of interest exists in the submission of this manuscript.

ABSTRACT

Neural remodeling after myocardial infarction (MI) may cause malignant ventricular arrhythmia, which is the main cause of sudden cardiac death following MI. Herein, we aimed to examine whether induced pluripotent stem cells (iPSc) transplantation can ameliorate neural remodeling and reduce ventricular arrhythmias (VA) in a post-infarcted swine model. Left anterior descending coronary arteries were balloon-occluded to generate MI. Animals were then divided into Sham, PBS control, and iPS groups. Dynamic electrocardiography programmed electric stimulation were performed to evaluate VA. The spatial distribution of vascularization, Cx43 and autonomic nerve regeneration were evaluated by immunofluorescence staining. Associated protein expression was detected by Western blotting. Likewise, we measured the enzymatic activities of superoxide dismutase and content of malondialdehyde. Six weeks later, the number of blood vessels increased significantly in the iPSc group. The expression of vascular endothelial growth factor and connexin 43 in the iPS group was significantly higher than the PBS group; however, the levels of nerve growth factor and tyrosine hydroxylase were lower. The oxidative stress was ameliorated by iPSc transplantation. Moreover, the number of sympathetic nerves in the iPSc group was reduced, while the parasympathetic nerve fibers had no obvious change. The transplantation of iPSc also significantly decreased the low-/high-frequency ratio and arrhythmia score of programmed electric stimulation-induced VA. In conclusion, iPSc intramyocardial transplantation reduces vulnerability to VAs, and the mechanism was related to the remodeling amelioration of autonomic nerves and gap junctions. Moreover, possible mechanisms of iPSc transplantation in improving neural remodeling may be related to attenuated oxidative stress and inflammatory response. J. Cell. Biochem. 115: 531–539, 2014. © 2013 Wiley Periodicals, Inc.

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