Regeneration of the Cardiac Conduction System by Adipose Tissue-Derived Stem Cells

  • Takahashi Toshinao
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
  • Nagai Toshio
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
  • Kanda Masato
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
  • Liu Mei-Lan
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
  • Kondo Naomichi
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine
  • Naito Atsuhiko T
    Department of Cardiovascular Medicine, The University of Tokyo Hospital
  • Ogura Takehiko
    Department of Pharmacology, Chiba University Graduate School of Medicine
  • Nakaya Haruaki
    Department of Pharmacology, Chiba University Graduate School of Medicine
  • Lee Jong-Kook
    Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine
  • Komuro Issei
    Department of Cardiovascular Medicine, The University of Tokyo Hospital
  • Kobayashi Yoshio
    Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine

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Background:Adipose tissue is one of the sources of mesenchymal stem cells, which have the potential to differentiate into various types of cells, including myocytes. Whether brown adipose tissue (BAT)-derived cells might differentiate into the cardiac pacemaking-conducting cells, and have the potential to regenerate the cardiac conduction system (CCS), is investigated in this study.Methods and Results:BAT was isolated from the interscapular area of mice and enzymatically digested before culture. Round or fusiform cells showed spontaneous beating at 4–7 days after culturing of BAT-derived cells. Reverse transcriptase-polymerase chain reaction analysis and immunocytochemical analysis revealed that BAT-derived cells expressed several cardiomyocytes, the CCS and pacemaker (PM) cell marker genes and proteins. Patch-clamp techniques revealed that spontaneous electrical activity and the shape of the action potential showed properties of cardiac PM cells. Next, a complete atrioventricular (AV) block was created in mice and green fluorescent protein-positive (GFP (+)) BAT-derived cells were injected intramyocardially around the AV node. At 1 week after transplantation, 50% of BAT-derived cells injected mice showed a sinus rhythm or a 2:1 AV block. Immunohistochemical analysis revealed that injected GFP (+) cells were engrafted and some GFP (+) cells co-expressed several cardiac PM cell marker proteins.Conclusions:BAT-derived cells differentiate into the CCS and PM-like cells in vitro and in vivo, and may become a useful cell source for arrhythmia therapy. (Circ J 2015; 79: 2703–2712)

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  • Circulation Journal

    Circulation Journal 79 (12), 2703-2712, 2015

    一般社団法人 日本循環器学会

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