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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.


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Submitted April 19, 2004
Accepted July 24, 2004

Non-hematopoietic 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*

Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan; Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Shinjuku, Tokyo, Japan
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan; CREST-JST and Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
CREST-JST and Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan
Institute for Advanced Cardiac Therapeutics, Keio University School of Medicine, Shinjuku, Tokyo, Japan

* Corresponding author; email: kfukuda{at}sc.itc.keio.ac.jp.

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 two 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 G-CSF to mobilize stem cells to the damaged myocardium. At 8 weeks post-MI, from 100 specimens we counted only 3 EGFP+actinin+ cells in myocardium of CD34-KSL-SP cells-transplanted mice, but more than 5,000 EGFP+actinin+ cells in whole BM cell-transplanted mice, suggesting that most of EGFP+actinin+ cells derived from non-hematopoietic BM cells. Next, clonally purified non-hematopoietic mesenchymal stem cells (MSC), 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 MSC.


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