Circulation Research. 2002;91:1092-1102
doi: 10.1161/01.RES.0000046045.00846.B0
doi: 10.1161/01.RES.0000046045.00846.B0
© 2002 American Heart Association, Inc.
Reviews |
Stem Cells for Myocardial Regeneration
From the Genetics and Molecular Biology Branch (D.O.), National Human Genome Research Institute, NIH, Bethesda, Md; Laboratory of Molecular Biology (J.M.H.), Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md; and Laboratory of Cardiac Energetics (A.E.A.), National Heart, Lung, and Blood Institute, NIH, Bethesda, Md.
Correspondence to Donald Orlic, PhD, Associate Investigator, Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, 49 Convent Dr-4442, Bethesda, MD 20892-4442. E-mail dorlic{at}nhgri.nih.gov
Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation for transdifferentiation. However, data supporting stem cell plasticity are extensive and cannot be easily dismissed. Myocardial regeneration is perhaps the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes are generated in what was previously considered a postmitotic organ. On the basis of postmortem microscopic analysis, it is proposed that renewal is achieved by stem cells that infiltrate normal and infarcted myocardium. To further understand the role of stem cells in regeneration, it is incumbent on us to develop instrumentation and technologies to monitor myocardial repair over time in large animal models. This may be achieved by tracking labeled stem cells as they migrate into myocardial infarctions. In addition, we must begin to identify the environmental cues that are needed for stem cell trafficking and we must define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will we be able to regulate this process and begin to realize the full potential of stem cells in regenerative medicine.
Key Words: stem cells • plasticity • ischemia • infarction • myocardial regeneration
This article has been cited by other articles:
 |
|
 |
|
  A. M. Leone, M. Valgimigli, M. B. Giannico, V. Zaccone, M. Perfetti, D. D'Amario, A. G. Rebuzzi, and F. Crea From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells Eur. Heart J., April 2, 2009; 30(8): 890 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Tao, C.-P. Lau, H.-F. Tse, and G.-R. Li Regulation of cell proliferation by intermediate-conductance Ca2+-activated potassium and volume-sensitive chloride channels in mouse mesenchymal stem cells Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1409 - C1416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Derval, L. Barandon, P. Dufourcq, L. Leroux, J.-M. D. Lamaziere, D. Daret, T. Couffinhal, and C. Duplaa Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model. Eur. J. Cardiothorac. Surg., August 1, 2008; 34(2): 248 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Pijnappels, M. J. Schalij, A. A. Ramkisoensing, J. van Tuyn, A. A.F. de Vries, A. van der Laarse, D. L. Ypey, and D. E. Atsma Forced Alignment of Mesenchymal Stem Cells Undergoing Cardiomyogenic Differentiation Affects Functional Integration With Cardiomyocyte Cultures Circ. Res., July 18, 2008; 103(2): 167 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-C. Hung, Y. Suzuki, T. Urashima, A. Caffarelli, G. Hoyt, A. Y. Sheikh, A. C. Yeung, I. Weissman, R. C. Robbins, J. W.M. Bulte, et al. Multimodality Evaluation of the Viability of Stem Cells Delivered Into Different Zones of Myocardial Infarction Circ Cardiovasc Imaging, July 1, 2008; 1(1): 6 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Medina, R. T. Kilani, N. Carr, E. Brown, and A. Ghahary Transdifferentiation of Peripheral Blood Mononuclear Cells into Epithelial-Like Cells Am. J. Pathol., October 1, 2007; 171(4): 1140 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. L. Tang and M. I. Phillips Invited commentary Ann. Thorac. Surg., April 1, 2007; 83(4): 1499 - 1500. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Behfar, C. Perez-Terzic, R. S. Faustino, D. K. Arrell, D. M. Hodgson, S. Yamada, M. Puceat, N. Niederlander, A. E Alekseev, L. V. Zingman, et al. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair J. Exp. Med., February 19, 2007; 204(2): 405 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kutschka, I. Y. Chen, T. Kofidis, T. Arai, G. von Degenfeld, A. Y. Sheikh, S. L. Hendry, J. Pearl, G. Hoyt, R. Sista, et al. Collagen Matrices Enhance Survival of Transplanted Cardiomyoblasts and Contribute to Functional Improvement of Ischemic Rat Hearts Circulation, July 4, 2006; 114(1_suppl): I-167 - I-173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Kutschka, T. Kofidis, I. Y. Chen, G. von Degenfeld, M. Zwierzchoniewska, G. Hoyt, T. Arai, D. R. Lebl, S. L. Hendry, A. Y. Sheikh, et al. Adenoviral Human BCL-2 Transgene Expression Attenuates Early Donor Cell Death After Cardiomyoblast Transplantation Into Ischemic Rat Hearts Circulation, July 4, 2006; 114(1_suppl): I-174 - I-180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Semenza Therapeutic Angiogenesis: Another Passing Phase? Circ. Res., May 12, 2006; 98(9): 1115 - 1116. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Baks, R.-J. van Geuns, E. Biagini, P. Wielopolski, N. R. Mollet, F. Cademartiri, W. J. van der Giessen, G. P. Krestin, P. W. Serruys, D. J. Duncker, et al. Effects of Primary Angioplasty for Acute Myocardial Infarction on Early and Late Infarct Size and Left Ventricular Wall Characteristics J. Am. Coll. Cardiol., January 3, 2006; 47(1): 40 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Baks, R.-J. van Geuns, E. Biagini, P. Wielopolski, N. R. Mollet, F. Cademartiri, W. J. van der Giessen, G. P. Krestin, P. W. Serruys, D. J. Duncker, et al. Effects of Primary Angioplasty for Acute Myocardial Infarction on Early and Late Infarct Size and Left Ventricular Wall Characteristics J. Am. Coll. Cardiol., December 13, 2005; (2005) j.jacc.2005.09.008v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. M. Leone, S. Rutella, G. Bonanno, A. Abbate, A. G. Rebuzzi, S. Giovannini, M. Lombardi, L. Galiuto, G. Liuzzo, F. Andreotti, et al. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function Eur. Heart J., June 2, 2005; 26(12): 1196 - 1204. [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]
|
|
|
|
|
|
S. Zhang, D. Wang, Z. Estrov, S. Raj, J. T. Willerson, and E. T.H. Yeh Both Cell Fusion and Transdifferentiation Account for the Transformation of Human Peripheral Blood CD34-Positive Cells Into Cardiomyocytes In Vivo Circulation, December 21, 2004; 110(25): 3803 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tamamori-Adachi, K. Hayashida, K. Nobori, C. Omizu, K. Yamada, N. Sakamoto, T. Kamura, K. Fukuda, S. Ogawa, K. I. Nakayama, et al. Down-regulation of p27Kip1 Promotes Cell Proliferation of Rat Neonatal Cardiomyocytes Induced by Nuclear Expression of Cyclin D1 and CDK4: EVIDENCE FOR IMPAIRED Skp2-DEPENDENT DEGRADATION OF p27 IN TERMINAL DIFFERENTIATION J. Biol. Chem., November 26, 2004; 279(48): 50429 - 50436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Y.W. Lew Mobilizing cells to the injured myocardium: A novel rescue strategy or an unwelcome intrusion? J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1521 - 1522. [Full Text] [PDF]
|
|
|
|
|
|
L. Barandon, T. Couffinhal, P. Dufourcq, P. Alzieu, D. Daret, C. Deville, and C. Duplaa Repair of Myocardial Infarction by Epicardial Deposition of Bone Marrow Cell-Coated Muscle Patch in a Murine Model Ann. Thorac. Surg., October 1, 2004; 78(4): 1409 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Edelman Contrast-enhanced MR Imaging of the Heart: Overview of the Literature Radiology, September 1, 2004; 232(3): 653 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Hodgson, A. Behfar, L. V. Zingman, G. C. Kane, C. Perez-Terzic, A. E. Alekseev, M. Puceat, and A. Terzic Stable benefit of embryonic stem cell therapy in myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H471 - H479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Ott, S. Berjukow, R. Marksteiner, E. Margreiter, G. Bock, G. Laufer, and S. Hering On the fate of skeletal myoblasts in a cardiac environment: down-regulation of voltage-gated ion channels J. Physiol., August 1, 2004; 558(3): 793 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. MELO, A. S. PACHORI, D. KONG, M. GNECCHI, K. WANG, R. E. PRATT, and V. J. DZAU Gene and cell-based therapies for heart disease FASEB J, April 1, 2004; 18(6): 648 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Heng, H. K. Haider, E. K.-W. Sim, T. Cao, and S. C. Ng Strategies for directing the differentiation of stem cells into the cardiomyogenic lineage in vitro Cardiovasc Res, April 1, 2004; 62(1): 34 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Serrano and V. Andres Telomeres and Cardiovascular Disease: Does Size Matter? Circ. Res., March 19, 2004; 94(5): 575 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Capogrossi Cardiac Stem Cells Fail With Aging: A New Mechanism for the Age-Dependent Decline in Cardiac Function Circ. Res., March 5, 2004; 94(4): 411 - 413. [Full Text] [PDF]
|
|
|
|
|
|
F. A. Jaffer and R. Weissleder Seeing Within: Molecular Imaging of the Cardiovascular System Circ. Res., March 5, 2004; 94(4): 433 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ozbaran, S. B. Omay, S. Nalbantgil, H. Kultursay, K. Kumanlioglu, D. Nart, and E. Pektok Autologous peripheral stem cell transplantation in patients with congestive heart failure due to ischemic heart disease Eur. J. Cardiothorac. Surg., March 1, 2004; 25(3): 342 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Barandon Editorial comment: Cellular cardiomyoplasty: 'inject is easy, demonstrate is complicated' Eur. J. Cardiothorac. Surg., March 1, 2004; 25(3): 350 - 351. [Full Text] [PDF]
|
|
|
|
|
|
V. Planat-Benard, C. Menard, M. Andre, M. Puceat, A. Perez, J.-M. Garcia-Verdugo, L. Penicaud, and L. Casteilla Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells Circ. Res., February 6, 2004; 94(2): 223 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-F. Xiao, J.-Y. Min, and J. P. Morgan Immunosuppression and xenotransplantation of cells for cardiac repair Ann. Thorac. Surg., February 1, 2004; 77(2): 737 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Heubach, E. M. Graf, J. Leutheuser, M. Bock, B. Balana, I. Zahanich, T. Christ, S. Boxberger, E. Wettwer, and U. Ravens Electrophysiological properties of human mesenchymal stem cells J. Physiol., February 1, 2004; 554(3): 659 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Braunwald Cardiology: the past, the present, and the future J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2031 - 2041. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Wu, I. Y. Chen, G. Sundaresan, J.-J. Min, A. De, J.-H. Qiao, M. C. Fishbein, and S. S. Gambhir Molecular Imaging of Cardiac Cell Transplantation in Living Animals Using Optical Bioluminescence and Positron Emission Tomography Circulation, September 16, 2003; 108(11): 1302 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Forrester, M. J. Price, and R. R. Makkar Stem Cell Repair of Infarcted Myocardium: An Overview for Clinicians Circulation, September 2, 2003; 108(9): 1139 - 1145. [Full Text] [PDF]
|
|
|
|
|
|
I. M. Barbash, P. Chouraqui, J. Baron, M. S. Feinberg, S. Etzion, A. Tessone, L. Miller, E. Guetta, D. Zipori, L. H. Kedes, et al. Systemic Delivery of Bone Marrow-Derived Mesenchymal Stem Cells to the Infarcted Myocardium: Feasibility, Cell Migration, and Body Distribution Circulation, August 19, 2003; 108(7): 863 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Caplice and B. J. Gersh Stem Cells to Repair the Heart: A Clinical Perspective Circ. Res., January 10, 2003; 92(1): 6 - 8. [Full Text] [PDF]
|
|