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, Keiichi Fukuda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)3581-3587
Number of pages7
JournalBlood
Volume104
Issue number12
DOIs
Publication statusPublished - 2004 Dec 1

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Stem cells
Mesenchymal Stromal Cells
Cardiac Myocytes
Bone
Actinin
Myocardial Infarction
Bone Marrow Cells
Myocardium
Bone Marrow
Transplants
Granulocyte Colony-Stimulating Factor
Side-Population Cells
enhanced green fluorescent protein
Regeneration
Stem Cells
Animals
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. / Kawada, Hiroshi; Fujita, Jun; Kinjo, Kentaro; Matsuzaki, Yumi; Tsuma, Mitsuyo; Miyatake, Hiroko; Muguruma, Yukari; Tsuboi, Kosuke; Itabashi, Yuji; Ikeda, Yasuo; Ogawa, Satoshi; Okano, Hideyuki; Hotta, Tomomitsu; Ando, Kiyoshi; Fukuda, Keiichi.

In: Blood, Vol. 104, No. 12, 01.12.2004, p. 3581-3587.

Research output: Contribution to journalArticle

Kawada, H, Fujita, J, Kinjo, K, Matsuzaki, Y, Tsuma, M, Miyatake, H, Muguruma, Y, Tsuboi, K, Itabashi, Y, Ikeda, Y, Ogawa, S, Okano, H, Hotta, T, Ando, K & Fukuda, K 2004, 'Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction', Blood, vol. 104, no. 12, pp. 3581-3587. https://doi.org/10.1182/blood-2004-04-1488
Kawada, Hiroshi ; Fujita, Jun ; Kinjo, Kentaro ; Matsuzaki, Yumi ; Tsuma, Mitsuyo ; Miyatake, Hiroko ; Muguruma, Yukari ; Tsuboi, Kosuke ; Itabashi, Yuji ; Ikeda, Yasuo ; Ogawa, Satoshi ; Okano, Hideyuki ; Hotta, Tomomitsu ; Ando, Kiyoshi ; Fukuda, Keiichi. / Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. In: Blood. 2004 ; Vol. 104, No. 12. pp. 3581-3587.
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AU - Miyatake, Hiroko

AU - Muguruma, Yukari

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AU - Ikeda, Yasuo

AU - Ogawa, Satoshi

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