|
|
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.
Previous Article | Next Article 
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.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
Related Article in Blood Online:
-
Time to end the stem cell wars?
- Darwin J. Prockop
Blood 2004 104: 3421-3422.
[Full Text]
[PDF]
This article has been cited by other articles:

|
 |

|
 |
 
M. Kumamoto, T. Nishiwaki, N. Matsuo, H. Kimura, and K. Matsushima
Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung injury
Eur. Respir. J.,
September 1, 2009;
34(3):
740 - 748.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sioud and Y. Floisand
NOD2/CARD15 on bone marrow CD34+ hematopoietic cells mediates induction of cytokines and cell differentiation
J. Leukoc. Biol.,
June 1, 2009;
85(6):
939 - 946.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Hiraumi, E. Iwai-Kanai, S. Baba, Y. Yui, Y. Kamitsuji, Y. Mizushima, H. Matsubara, M. Watanabe, K.-i. Watanabe, S. Toyokuni, et al.
Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury
Am J Physiol Heart Circ Physiol,
March 1, 2009;
296(3):
H823 - H832.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. C. Vela, G. V. Silva, J. A.R. Assad, A. L.S. Sousa, S. Coulter, M. R. Fernandes, E. C. Perin, J. T. Willerson, and L. M. Buja
Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs
J. Histochem. Cytochem.,
February 1, 2009;
57(2):
167 - 176.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Walker, S. K. Shah, M. T. Harting, and C. S. Cox Jr
Progenitor cell therapies for traumatic brain injury: barriers and opportunities in translation
Dis. Model. Mech.,
January 1, 2009;
2(1-2):
23 - 38.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sasaki, R. Abe, Y. Fujita, S. Ando, D. Inokuma, and H. Shimizu
Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type
J. Immunol.,
February 15, 2008;
180(4):
2581 - 2587.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.-H. Wang, W.-J. Cherng, N.-I Yang, L.-T. Kuo, C.-M. Hsu, H.-I Yeh, Y.-J. Lan, C.-H. Yeh, and W. L. Stanford
Late-Outgrowth Endothelial Cells Attenuate Intimal Hyperplasia Contributed by Mesenchymal Stem Cells After Vascular Injury
Arterioscler Thromb Vasc Biol,
January 1, 2008;
28(1):
54 - 60.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Tao, C.-P. Lau, H.-F. Tse, and G.-R. Li
Functional ion channels in mouse bone marrow mesenchymal stem cells
Am J Physiol Cell Physiol,
November 1, 2007;
293(5):
C1561 - C1567.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Endo, M. Sano, J. Fujita, K. Hayashida, S. Yuasa, N. Aoyama, Y. Takehara, O. Kato, S. Makino, S. Ogawa, et al.
Bone Marrow-Derived Cells Are Involved in the Pathogenesis of Cardiac Hypertrophy in Response to Pressure Overload
Circulation,
September 4, 2007;
116(10):
1176 - 1184.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Ip, Y. Wu, J. Huang, L. Zhang, R. E. Pratt, and V. J. Dzau
Mesenchymal Stem Cells Use Integrin beta1 Not CXC Chemokine Receptor 4 for Myocardial Migration and Engraftment
Mol. Biol. Cell,
August 1, 2007;
18(8):
2873 - 2882.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Prevosto, M. Zancolli, P. Canevali, M. R. Zocchi, and A. Poggi
Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction
Haematologica,
July 1, 2007;
92(7):
881 - 888.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. G. Zenovich and D. A. Taylor
CELL THERAPY IN KIDNEY DISEASE: CAUTIOUS OPTIMISM... BUT OPTIMISM NONETHELESS
Perit. Dial. Int.,
June 1, 2007;
27(Supplement_2):
S94 - S103.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Abdel-Latif, R. Bolli, I. M. Tleyjeh, V. M. Montori, E. C. Perin, C. A. Hornung, E. K. Zuba-Surma, M. Al-Mallah, and B. Dawn
Adult Bone Marrow-Derived Cells for Cardiac Repair: A Systematic Review and Meta-analysis
Arch Intern Med,
May 28, 2007;
167(10):
989 - 997.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Tateishi, E. Ashihara, N. Takehara, T. Nomura, S. Honsho, T. Nakagami, S. Morikawa, T. Takahashi, T. Ueyama, H. Matsubara, et al.
Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration
J. Cell Sci.,
May 15, 2007;
120(10):
1791 - 1800.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Ries, V. Egea, M. Karow, H. Kolb, M. Jochum, and P. Neth
MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines
Blood,
May 1, 2007;
109(9):
4055 - 4063.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. De Becker, P. Van Hummelen, M. Bakkus, I. Vande Broek, J. De Wever, M. De Waele, and I. Van Riet
Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3
Haematologica,
April 1, 2007;
92(4):
440 - 449.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Pevsner-Fischer, V. Morad, M. Cohen-Sfady, L. Rousso-Noori, A. Zanin-Zhorov, S. Cohen, I. R. Cohen, and D. Zipori
Toll-like receptors and their ligands control mesenchymal stem cell functions
Blood,
February 15, 2007;
109(4):
1422 - 1432.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Sato, K. Ozaki, I. Oh, A. Meguro, K. Hatanaka, T. Nagai, K. Muroi, and K. Ozawa
Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells
Blood,
January 1, 2007;
109(1):
228 - 234.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ince, T. C. Rehders, S. Kische, S. Drawert, E. Adolf, T. Kleinfeldt, M. Petzsch, and C. A. Nienaber
G-CSF in the setting of acute myocardial infarction
Eur. Heart J. Suppl.,
December 1, 2006;
8(suppl_H):
H40 - H45.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Jiang, H. Kh. Haider, N. M. Idris, A. Salim, and M. Ashraf
Supportive Interaction Between Cell Survival Signaling and Angiocompetent Factors Enhances Donor Cell Survival and Promotes Angiomyogenesis for Cardiac Repair
Circ. Res.,
September 29, 2006;
99(7):
776 - 784.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Lehrke, R. Mazhari, D. J. Durand, M. Zheng, D. Bedja, J. M. Zimmet, K. H. Schuleri, A. S. Chi, K. L. Gabrielson, and J. M. Hare
Aging Impairs the Beneficial Effect of Granulocyte Colony-Stimulating Factor and Stem Cell Factor on Post-Myocardial Infarction Remodeling
Circ. Res.,
September 1, 2006;
99(5):
553 - 560.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Anversa, A. Leri, and J. Kajstura
Cardiac Regeneration
J. Am. Coll. Cardiol.,
May 2, 2006;
47(9):
1769 - 1776.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Fukuda and S. Yuasa
Stem Cells as a Source of Regenerative Cardiomyocytes
Circ. Res.,
April 28, 2006;
98(8):
1002 - 1013.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Dawn, Y. Guo, A. Rezazadeh, Y. Huang, A. B. Stein, G. Hunt, S. Tiwari, J. Varma, Y. Gu, S. D. Prabhu, et al.
Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function
Circ. Res.,
April 28, 2006;
98(8):
1098 - 1105.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Juthier, A. Vincentelli, J. Gaudric, D. Corseaux, O. Fouquet, C. Calet, T. L. Tourneau, V. Soenen, C. Zawadzki, O. Fabre, et al.
Decellularized heart valve as a scaffold for in vivo recellularization: Deleterious effects of granulocyte colony-stimulating factor
J. Thorac. Cardiovasc. Surg.,
April 1, 2006;
131(4):
843 - 852.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Gnecchi, H. He, N. Noiseux, O. D. Liang, L. Zhang, F. Morello, H. Mu, L. G. Melo, R. E. Pratt, J. S. Ingwall, et al.
Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement
FASEB J,
April 1, 2006;
20(6):
661 - 669.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Yoshioka, M. Takahashi, Y. Shiba, C. Suzuki, H. Morimoto, A. Izawa, H. Ise, and U. Ikeda
Granulocyte colony-stimulating factor (G-CSF) accelerates reendothelialization and reduces neointimal formation after vascular injury in mice
Cardiovasc Res,
April 1, 2006;
70(1):
61 - 69.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Kanellakis, N. J. Slater, X.-J. Du, A. Bobik, and D. J. Curtis
Granulocyte colony-stimulating factor and stem cell factor improve endogenous repair after myocardial infarction
Cardiovasc Res,
April 1, 2006;
70(1):
117 - 125.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. M.A. Lombaert, P. K. Wierenga, T. Kok, H. H. Kampinga, G. deHaan, and R. P. Coppes
Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands.
Clin. Cancer Res.,
March 15, 2006;
12(6):
1804 - 1812.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Chan-Ling, L. Baxter, A. Afzal, N. Sengupta, S. Caballero, E. Rosinova, and M. B. Grant
Hematopoietic Stem Cells Provide Repair Functions after Laser-Induced Bruch's Membrane Rupture Model of Choroidal Neovascularization
Am. J. Pathol.,
March 1, 2006;
168(3):
1031 - 1044.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Muguruma, T. Yahata, H. Miyatake, T. Sato, T. Uno, J. Itoh, S. Kato, M. Ito, T. Hotta, and K. Ando
Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment
Blood,
March 1, 2006;
107(5):
1878 - 1887.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Kawada, S. Takizawa, T. Takanashi, Y. Morita, J. Fujita, K. Fukuda, S. Takagi, H. Okano, K. Ando, and T. Hotta
Administration of Hematopoietic Cytokines in the Subacute Phase After Cerebral Infarction Is Effective for Functional Recovery Facilitating Proliferation of Intrinsic Neural Stem/Progenitor Cells and Transition of Bone Marrow-Derived Neuronal Cells
Circulation,
February 7, 2006;
113(5):
701 - 710.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Kawada, J. Fujita, M. Tsuma, Y. Matsuzaki, H. Okano, K. Fukuda, T. Hotta, and K. Ando
Cardiac Myofibroblasts of Hematopoietic Origin Are Mobilized by G-CSF and Contribute to Cardiac Repair after Myocardial Infarction.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
1699 - 1699.
[Abstract]
|
 |
|

|
 |

|
 |
 
A. Poggi, C. Prevosto, A.-M. Massaro, S. Negrini, S. Urbani, I. Pierri, R. Saccardi, M. Gobbi, and M. R. Zocchi
Interaction between Human NK Cells and Bone Marrow Stromal Cells Induces NK Cell Triggering: Role of NKp30 and NKG2D Receptors
J. Immunol.,
November 15, 2005;
175(10):
6352 - 6360.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Leri, J. Kajstura, and P. Anversa
Cardiac Stem Cells and Mechanisms of Myocardial Regeneration
Physiol Rev,
October 1, 2005;
85(4):
1373 - 1416.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Ince, M. Petzsch, H. D. Kleine, H. Eckard, T. Rehders, D. Burska, S. Kische, M. Freund, and C. A. Nienaber
Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction: Final 1-year Results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial
Circulation,
August 30, 2005;
112(9_suppl):
I-73 - I-80.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Patrawala, T. Calhoun, R. Schneider-Broussard, J. Zhou, K. Claypool, and D. G. Tang
Side Population Is Enriched in Tumorigenic, Stem-Like Cancer Cells, whereas ABCG2+ and ABCG2- Cancer Cells Are Similarly Tumorigenic
Cancer Res.,
July 15, 2005;
65(14):
6207 - 6219.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. K. Haider and M. Ashraf
Bone marrow stem cell transplantation for cardiac repair
Am J Physiol Heart Circ Physiol,
June 1, 2005;
288(6):
H2557 - H2567.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Galli, A. Innocenzi, L. Staszewsky, L. Zanetta, M. Sampaolesi, A. Bai, E. Martinoli, E. Carlo, G. Balconi, F. Fiordaliso, et al.
Mesoangioblasts, Vessel-Associated Multipotent Stem Cells, Repair the Infarcted Heart by Multiple Cellular Mechanisms: A Comparison With Bone Marrow Progenitors, Fibroblasts, and Endothelial Cells
Arterioscler Thromb Vasc Biol,
April 1, 2005;
25(4):
692 - 697.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. K. Zhang and D. K. Watson
The FLI-1 Transcription Factor Is a Short-Lived Phosphoprotein in T Cells
J. Biochem.,
March 1, 2005;
137(3):
297 - 302.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. C. Wollert and H. Drexler
Clinical Applications of Stem Cells for the Heart
Circ. Res.,
February 4, 2005;
96(2):
151 - 163.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|