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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3581-3587. Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-04-1488. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1488v1 104/12/3581    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kawada, H. Articles by Fukuda, K. Search for Related Content PubMed PubMed Citation Articles by Kawada, H. Articles by Fukuda, K. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction Hiroshi Kawada, Jun Fujita, Kentaro Kinjo, Yumi Matsuzaki, Mitsuyo Tsuma, Hiroko Miyatake, Yukari Muguruma, Kosuke Tsuboi, Yuji Itabashi, Yasuo Ikeda, Satoshi Ogawa, Hideyuki Okano, Tomomitsu Hotta, Kiyoshi Ando, and 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. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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