Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction

  • Hiroshi Kawada
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Jun Fujita
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Kentaro Kinjo
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Yumi Matsuzaki
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Mitsuyo Tsuma
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Hiroko Miyatake
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Yukari Muguruma
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Kosuke Tsuboi
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Yuji Itabashi
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Yasuo Ikeda
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Satoshi Ogawa
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Hideyuki Okano
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Tomomitsu Hotta
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Kiyoshi Ando
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.
  • Keiichi Fukuda
    From the Division of Hematology, the Department of Medicine, Tokai University School of Medicine; Research Center for Regenerative Medicine, Tokai University School of Medicine; the Department of Internal Medicine, Keio University School of Medicine; the Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine; Core Research for Evolutional Science and Technology-Japan Science and Technology and Department of Physiology, Keio University School of Medicine, Japan.

抄録

<jats:p>Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)–derived cardiomyocytes. First, we transplanted single CD34– c-kit+Sca-1+ lineage– side population (CD34–KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP+ actinin+ cells in myocardium of CD34– KSL-SP cells in mice that received transplants, but more than 5000 EGFP+ actinin+ cells in whole BM cell in mice that received transplants, suggesting that most of EGFP+ actinin+ cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP+ actinin+ cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.</jats:p>

収録刊行物

  • Blood

    Blood 104 (12), 3581-3587, 2004-12-01

    American Society of Hematology

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