Circulation. 2002;105:93-98
doi: 10.1161/hc0102.101442
doi: 10.1161/hc0102.101442
(Circulation. 2002;105:93.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart
From the Department of Medicine, Division of Cardiology, Johns Hopkins School of Medicine (C.T., P.D.K.), and Osiris Therapeutics, Inc (M.F.P.), Baltimore, Md; and the Powell Gene Therapy Center, Departments of Pediatrics, Molecular Genetics, and Microbiology, University of Florida School of Medicine, Gainesville, Fla (K.S.C., B.J.B.).
Correspondence to Mark Pittenger, PhD, Osiris Therapeutics Inc, 2001 Aliceanna St, Baltimore, MD 21231. E-mail mpittenger{at}osiristx.com
Background— Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium.
Methods and Results— A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ, were injected into the left ventricle of CB17 SCID/beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, ß-myosin heavy chain, 
-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs.
Conclusions— The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.
Key Words: stem cells • genes • myocytes • heart failure
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J. J. Gavira, J. Herreros, A. Perez, M. J. Garcia-Velloso, J. Barba, F. Martin-Herrero, C. Canizo, A. Martin-Arnau, J. M. Marti-Climent, M. Hernandez, et al. Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up J. Thorac. Cardiovasc. Surg., April 1, 2006; 131(4): 799 - 804. [Abstract] [Full Text] [PDF]
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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]
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S. Francois, M. Bensidhoum, M. Mouiseddine, C. Mazurier, B. Allenet, A. Semont, J. Frick, A. Sache, S. Bouchet, D. Thierry, et al. Local Irradiation Not Only Induces Homing of Human Mesenchymal Stem Cells at Exposed Sites but Promotes Their Widespread Engraftment to Multiple Organs: A Study of Their Quantitative Distribution After Irradiation Damage Stem Cells, April 1, 2006; 24(4): 1020 - 1029. [Abstract] [Full Text] [PDF]
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X. Wang, Q. Hu, A. Mansoor, J. Lee, Z. Wang, T. Lee, A. H. L. From, and J. Zhang Bioenergetic and functional consequences of stem cell-based VEGF delivery in pressure-overloaded swine hearts Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1393 - H1405. [Abstract] [Full Text] [PDF]
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J. Stagg, S. Pommey, N. Eliopoulos, and J. Galipeau Interferon-{gamma}-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell Blood, March 15, 2006; 107(6): 2570 - 2577. [Abstract] [Full Text] [PDF]
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G. M. Spaggiari, A. Capobianco, S. Becchetti, M. C. Mingari, and L. Moretta Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation Blood, February 15, 2006; 107(4): 1484 - 1490. [Abstract] [Full Text] [PDF]
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Y. Ma, Y. Xu, Z. Xiao, W. Yang, C. Zhang, E. Song, Y. Du, and L. Li Reconstruction of Chemically Burned Rat Corneal Surface by Bone Marrow-Derived Human Mesenchymal Stem Cells Stem Cells, February 1, 2006; 24(2): 315 - 321. [Abstract] [Full Text] [PDF]
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M. Krampera, L. Cosmi, R. Angeli, A. Pasini, F. Liotta, A. Andreini, V. Santarlasci, B. Mazzinghi, G. Pizzolo, F. Vinante, et al. Role for Interferon-{gamma} in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells Stem Cells, February 1, 2006; 24(2): 386 - 398. [Abstract] [Full Text] [PDF]
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W. Zhu, J. Chen, X. Cong, S. Hu, and X. Chen Hypoxia and Serum Deprivation-Induced Apoptosis in Mesenchymal Stem Cells Stem Cells, February 1, 2006; 24(2): 416 - 425. [Abstract] [Full Text] [PDF]
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J. J. Minguell and A. Erices Mesenchymal Stem Cells and the Treatment of Cardiac Disease Experimental Biology and Medicine, January 1, 2006; 231(1): 39 - 49. [Abstract] [Full Text] [PDF]
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J. Andrade, J. T. Lam, M. Zamora, C. Huang, D. Franco, N. Sevilla, P. J. Gruber, J. T. Lu, and P. Ruiz-Lozano Predominant fusion of bone marrow-derived cardiomyocytes Cardiovasc Res, December 1, 2005; 68(3): 387 - 393. [Abstract] [Full Text] [PDF]
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C. E. Murry, L. J. Field, and P. Menasche Cell-Based Cardiac Repair: Reflections at the 10-Year Point Circulation, November 15, 2005; 112(20): 3174 - 3183. [Full Text] [PDF]
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Y. L. Tang, Y. Tang, Y. C. Zhang, K. Qian, L. Shen, and M. I. Phillips Improved Graft Mesenchymal Stem Cell Survival in Ischemic Heart With a Hypoxia-Regulated Heme Oxygenase-1 Vector J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1339 - 1350. [Abstract] [Full Text] [PDF]
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V. J. Dzau, M. Gnecchi, and A. S. Pachori Enhancing Stem Cell Therapy Through Genetic Modification J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1351 - 1353. [Full Text] [PDF]
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D. L. Kraitchman, M. Tatsumi, W. D. Gilson, T. Ishimori, D. Kedziorek, P. Walczak, W. P. Segars, H. H. Chen, D. Fritzges, I. Izbudak, et al. Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction Circulation, September 6, 2005; 112(10): 1451 - 1461. [Abstract] [Full Text] [PDF]
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T. Tondreau, N. Meuleman, A. Delforge, M. Dejeneffe, R. Leroy, M. Massy, C. Mortier, D. Bron, and L. Lagneaux Mesenchymal Stem Cells Derived from CD133-Positive Cells in Mobilized Peripheral Blood and Cord Blood: Proliferation, Oct4 Expression, and Plasticity Stem Cells, September 1, 2005; 23(8): 1105 - 1112. [Abstract] [Full Text] [PDF]
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N. Nagaya, K. Kangawa, T. Itoh, T. Iwase, S. Murakami, Y. Miyahara, T. Fujii, M. Uematsu, H. Ohgushi, M. Yamagishi, et al. Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy Circulation, August 23, 2005; 112(8): 1128 - 1135. [Abstract] [Full Text] [PDF]
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M. Siepe, C. Heilmann, P. von Samson, P. Menasche, and F. Beyersdorf Stem cell research and cell transplantation for myocardial regeneration Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 318 - 324. [Abstract] [Full Text] [PDF]
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C. Muscari, F. Bonafe, I. Stanic, F. Flamigni, C. Stefanelli, G. Farruggia, C. Guarnieri, and C. M. Caldarera Polyamine Depletion Reduces TNF{alpha}/MG132-Induced Apoptosis in Bone Marrow Stromal Cells Stem Cells, August 1, 2005; 23(7): 983 - 991. [Abstract] [Full Text] [PDF]
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C. Ventura Forced myocardin expression primes cardiac and smooth muscle transcription patterning in human mesenchymal stem cells Cardiovasc Res, August 1, 2005; 67(2): 182 - 183. [Full Text] [PDF]
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K. C. Wollert and H. Drexler Mesenchymal Stem Cells for Myocardial Infarction: Promises and Pitfalls Circulation, July 12, 2005; 112(2): 151 - 153. [Full Text] [PDF]
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O. Pelz, M. Wu, T. Nikolova, M. Kamprad, M. Ackermann, D. Egger, F. Emmrich, A. M. Wobus, and M. Cross Duplex Polymerase Chain Reaction Quantification of Human Cells in a Murine Background Stem Cells, June 1, 2005; 23(6): 828 - 833. [Abstract] [Full Text] [PDF]
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