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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S. Sartore, M. Lenzi, A. Angelini, A. Chiavegato, L. Gasparotto, P. D. Coppi, R. Bianco, and G. Gerosa Amniotic mesenchymal cells autotransplanted in a porcine model of cardiac ischemia do not differentiate to cardiogenic phenotypes Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 677 - 684. [Abstract] [Full Text] [PDF]
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S. Fazel, L. Chen, R. D. Weisel, D. Angoulvant, C. Seneviratne, A. Fazel, P. Cheung, J. Lam, P. W.M. Fedak, T. M. Yau, et al. Cell transplantation preserves cardiac function after infarction by infarct stabilization: Augmentation by stem cell factor J. Thorac. Cardiovasc. Surg., November 1, 2005; 130(5): 1310 - 1310. [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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L. C. Amado, A. P. Saliaris, K. H. Schuleri, M. St. John, J.-S. Xie, S. Cattaneo, D. J. Durand, T. Fitton, J. Q. Kuang, G. Stewart, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction PNAS, August 9, 2005; 102(32): 11474 - 11479. [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. 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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J. van Tuyn, S. Knaan-Shanzer, M. J.M. van de Watering, M. de Graaf, A. van der Laarse, M. J. Schalij, E. E. van der Wall, A. A.F. de Vries, and D. E. Atsma Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin Cardiovasc Res, August 1, 2005; 67(2): 245 - 255. [Abstract] [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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W. Dai, S. L. Hale, B. J. Martin, J.-Q. Kuang, J. S. Dow, L. E. Wold, and R. A. Kloner Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium: Short- and Long-Term Effects Circulation, July 12, 2005; 112(2): 214 - 223. [Abstract] [Full Text] [PDF]
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 F. Togel, Z. Hu, K. Weiss, J. Isaac, C. Lange, C. Westenfelder, T. Stasko, M.D. Brown, J.A. Carucci, S. Euvrard, et al. Amelioration of Acute Renal Failure by Stem Cell Therapy--Paracrine Secretion Versus Transdifferentiation into Resident Cells: Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005 J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1153 - 1163. [Full Text] [PDF]
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S. Aggarwal and M. F. Pittenger Human mesenchymal stem cells modulate allogeneic immune cell responses Blood, February 15, 2005; 105(4): 1815 - 1822. [Abstract] [Full Text] [PDF]
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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]
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R. F. Klees, R. M. Salasznyk, K. Kingsley, W. A. Williams, A. Boskey, and G. E. Plopper Laminin-5 Induces Osteogenic Gene Expression in Human Mesenchymal Stem Cells through an ERK-dependent Pathway Mol. Biol. Cell, February 1, 2005; 16(2): 881 - 890. [Abstract] [Full Text] [PDF]
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