Circulation Research. 2004;95:9-20
doi: 10.1161/01.RES.0000135902.99383.6f
doi: 10.1161/01.RES.0000135902.99383.6f
© 2004 American Heart Association, Inc.
Reviews |
Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics
From Osiris Therapeutics, Inc., Baltimore, Md.
Correspondence to Mark F. Pittenger, PhD, Osiris Therapeutics, Inc., 2001 Aliceanna St, Baltimore, MD 21231. E-mail mpittenger{at}osiristx.com
This Review is part of a thematic series on Stem Cells, which includes the following articles:
Differentiation of Pluripotent Embryonic Stem Cells Into Cardiomyocytes
Derivation and Potential Applications of Human Embryonic Stem Cells
Stem Cells for Myocardial Regeneration
Myocyte Death, Growth, and Regeneration in Cardiac Hypertrophy and Failure
Neural Stem Cells: An Overview
Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics
Therapeutics and Use of Stem Cells
Roberto Bolli Editors
Mesenchymal stem cells (MSCs) represent a stem cell population present in adult tissues that can be isolated, expanded in culture, and characterized in vitro and in vivo. MSCs differentiate readily into chondrocytes, adipocytes, osteocytes, and they can support hematopoietic stem cells or embryonic stem cells in culture. Evidence suggests MSCs can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocyte cells. When introduced into the infarcted heart, MSCs prevent deleterious remodeling and improve recovery, although further understanding of MSC differentiation in the cardiac scar tissue is still needed. MSCs have been injected directly into the infarct, or they have been administered intravenously and seen to home to the site of injury. Examination of the interaction of allogeneic MSCs with cells of the immune system indicates little rejection by T cells. Persistence of allogeneic MSCs in vivo suggests their potential "off the shelf" therapeutic use for multiple recipients. Clinical use of cultured human MSCs (hMSCs) has begun for cancer patients, and recipients have received autologous or allogeneic MSCs. Research continues to support the desirable traits of MSCs for development of cellular therapeutics for many tissues, including the cardiovascular system. In summary, hMSCs isolated from adult bone marrow provide an excellent model for development of stem cell therapeutics, and their potential use in the cardiovascular system is currently under investigation in the laboratory and clinical settings.
Key Words: cardiomyoplasty • mesenchymal • cell therapy • stem cell
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A. Schmidt, D. Ladage, T. Schinkothe, U. Klausmann, C. Ulrichs, F.-J. Klinz, K. Brixius, S. Arnhold, B. Desai, U. Mehlhorn, et al. Basic Fibroblast Growth Factor Controls Migration in Human Mesenchymal Stem Cells Stem Cells, July 1, 2006; 24(7): 1750 - 1758. [Abstract] [Full Text] [PDF]
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H. Okuyama, B. Krishnamachary, Y. F. Zhou, H. Nagasawa, M. Bosch-Marce, and G. L. Semenza Expression of Vascular Endothelial Growth Factor Receptor 1 in Bone Marrow-derived Mesenchymal Cells Is Dependent on Hypoxia-inducible Factor 1 J. Biol. Chem., June 2, 2006; 281(22): 15554 - 15563. [Abstract] [Full Text] [PDF]
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T. Freyman, G. Polin, H. Osman, J. Crary, M. Lu, L. Cheng, M. Palasis, and R. L. Wilensky A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction Eur. Heart J., May 1, 2006; 27(9): 1114 - 1122. [Abstract] [Full Text] [PDF]
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L. Zentilin, S. Tafuro, S. Zacchigna, N. Arsic, L. Pattarini, M. Sinigaglia, and M. Giacca Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels Blood, May 1, 2006; 107(9): 3546 - 3554. [Abstract] [Full Text] [PDF]
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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]
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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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V. F. M. Segers, I. Van Riet, L. J. Andries, K. Lemmens, M. J. Demolder, A. J. M. L. De Becker, M. M. Kockx, and G. W. De Keulenaer Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1370 - H1377. [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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K. Tamama, V. H. Fan, L. G. Griffith, H. C. Blair, and A. Wells Epidermal Growth Factor as a Candidate for Ex Vivo Expansion of Bone Marrow-Derived Mesenchymal Stem Cells Stem Cells, March 1, 2006; 24(3): 686 - 695. [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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M. Aluigi, M. Fogli, A. Curti, A. Isidori, E. Gruppioni, C. Chiodoni, M. P. Colombo, P. Versura, A. D'Errico-Grigioni, E. Ferri, et al. Nucleofection Is an Efficient Nonviral Transfection Technique for Human Bone Marrow-Derived Mesenchymal Stem Cells Stem Cells, February 1, 2006; 24(2): 454 - 461. [Abstract] [Full Text] [PDF]
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W. Su, H. Zhang, Z. Jia, C. Zhou, Y. Wei, and S. Hu Cartilage-Derived Stromal Cells: Is It a Novel Cell Resource for Cell Therapy to Regenerate Infarcted Myocardium? Stem Cells, February 1, 2006; 24(2): 349 - 356. [Abstract] [Full Text] [PDF]
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Y. Misao, G. Takemura, M. Arai, S. Sato, K. Suzuki, S. Miyata, K.-i. Kosai, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation Cardiovasc Res, February 1, 2006; 69(2): 476 - 490. [Abstract] [Full Text] [PDF]
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J. L. Spees, S. D. Olson, M. J. Whitney, and D. J. Prockop Mitochondrial transfer between cells can rescue aerobic respiration PNAS, January 31, 2006; 103(5): 1283 - 1288. [Abstract] [Full Text] [PDF]
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D. G. Phinney, K. Hill, C. Michelson, M. DuTreil, C. Hughes, S. Humphries, R. Wilkinson, M. Baddoo, and E. Bayly Biological Activities Encoded by the Murine Mesenchymal Stem Cell Transcriptome Provide a Basis for Their Developmental Potential and Broad Therapeutic Efficacy Stem Cells, January 1, 2006; 24(1): 186 - 198. [Abstract] [Full Text] [PDF]
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N. Riggi, L. Cironi, P. Provero, M.-L. Suva, K. Kaloulis, C. Garcia-Echeverria, F. Hoffmann, A. Trumpp, and I. Stamenkovic Development of Ewing's Sarcoma from Primary Bone Marrow-Derived Mesenchymal Progenitor Cells Cancer Res., December 15, 2005; 65(24): 11459 - 11468. [Abstract] [Full Text] [PDF]
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J. R. Munoz, B. R. Stoutenger, A. P. Robinson, J. L. Spees, and D. J. Prockop Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice PNAS, December 13, 2005; 102(50): 18171 - 18176. [Abstract] [Full Text] [PDF]
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S. L.M.A. Beeres, D. E. Atsma, A. van der Laarse, D. A. Pijnappels, J. van Tuyn, W. E. Fibbe, A. A.F. de Vries, D. L. Ypey, E. E. van der Wall, and M. J. Schalij Human Adult Bone Marrow Mesenchymal Stem Cells Repair Experimental Conduction Block in Rat Cardiomyocyte Cultures J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1943 - 1952. [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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