Circulation. 2002;106:3009-3017
Published online before print November 11, 2002, doi: 10.1161/01.CIR.0000043246.74879.CD
Published online before print November 11, 2002, doi: 10.1161/01.CIR.0000043246.74879.CD
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(Circulation. 2002;106:3009.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI)
From the Department of Molecular Cardiology and Department of Cardiology, Internal Medicine IV, (B.A., V.S., C.T., M.B., R.L., A.A., C.U.), Department of Nuclear Medicine (N.D., F.G.), and the Department of Hematology (H.M., D.H.), University of Frankfurt, Frankfurt, Germany.
Correspondence to Andreas M. Zeiher, MD, and Stefanie Dimmeler, PhD, Internal Medicine IV, University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Dimmeler{at}em.uni-frankfurt.de or zeiher@em.uni-frankfurt.de
Background— Experimental studies suggest that transplantation of blood-derived or bone marrow–derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown.
Methods and Results— We randomly allocated 20 patients with reperfused acute myocardial infarction (AMI) to receive intracoronary infusion of either bone marrow–derived (n=9) or circulating blood–derived progenitor cells (n=11) into the infarct artery 4.3±1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6±9.6% to 60.1±8.6% (P=0.003), improved regional wall motion in the infarct zone (-1.5±0.2 to -0.5±0.7 SD/chord; P<0.001), and profoundly reduced end-systolic left ventricular volumes (56.1±20 mL to 42.2±15.1 mL; P=0.01) at 4-month follow-up. In contrast, in a nonrandomized matched reference group, left ventricular ejection fraction only slightly increased from 51±10% to 53.5±7.9%, and end-systolic volumes remained unchanged. Echocardiography revealed a profound enhancement of regional contractile function (wall motion score index 1.4±0.2 at baseline versus 1.19±0.2 at follow-up; P<0.001). At 4 months, coronary blood flow reserve was significantly (P<0.001) increased in the infarct artery. Quantitative F-18-fluorodeoxyglucose–positron emission tomography analysis revealed a significant (P<0.01) increase in myocardial viability in the infarct zone. There were no differences for any measured parameter between blood-derived or bone marrow–derived progenitor cells. No signs of an inflammatory response or malignant arrhythmias were observed.
Conclusions— In patients with AMI, intracoronary infusion of autologous progenitor cells appears to be feasible and safe and may beneficially affect postinfarction remodeling processes.
Key Words: myocardial infarction • cells • remodeling • transplantation
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 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]
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S. Erbs, A. Linke, V. Schachinger, B. Assmus, H. Thiele, K.-W. Diederich, C. Hoffmann, S. Dimmeler, T. Tonn, R. Hambrecht, et al. Restoration of Microvascular Function in the Infarct-Related Artery by Intracoronary Transplantation of Bone Marrow Progenitor Cells in Patients With Acute Myocardial Infarction: The Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) Trial Circulation, July 24, 2007; 116(4): 366 - 374. [Abstract] [Full Text] [PDF]
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R. K. Cheng, T. Asai, H. Tang, N. H. Dashoush, R. J. Kara, K. D. Costa, Y. Naka, E. X. Wu, D. J. Wolgemuth, and H. W. Chaudhry Cyclin A2 Induces Cardiac Regeneration After Myocardial Infarction and Prevents Heart Failure Circ. Res., June 22, 2007; 100(12): 1741 - 1748. [Abstract] [Full Text] [PDF]
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 R. M Cubbon, A. Rajwani, and S. B Wheatcroft The impact of insulin resistance on endothelial function, progenitor cells and repair Diabetes and Vascular Disease Research, June 1, 2007; 4(2): 103 - 111. [Abstract] [PDF]
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 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]
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S. Zhang, J. Ge, L. Zhao, J. Qian, Z. Huang, L. Shen, A. Sun, K. Wang, and Y. Zou Host Vascular Niche Contributes to Myocardial Repair Induced by Intracoronary Transplantation of Bone Marrow CD34+ Progenitor Cells in Infarcted Swine Heart Stem Cells, May 1, 2007; 25(5): 1195 - 1203. [Abstract] [Full Text] [PDF]
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M. S. Penn Patient and Cellular Characteristics Determine Efficacy of Cell Therapy Circ. Res., April 27, 2007; 100(8): 1101 - 1103. [Full Text] [PDF]
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V. L.T. Ballard and J. M. Edelberg Stem Cells and the Regeneration of the Aging Cardiovascular System Circ. Res., April 27, 2007; 100(8): 1116 - 1127. [Abstract] [Full Text] [PDF]
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B. Assmus, U. Fischer-Rasokat, J. Honold, F. H. Seeger, S. Fichtlscherer, T. Tonn, E. Seifried, V. Schachinger, S. Dimmeler, and A. M. Zeiher Transcoronary Transplantation of Functionally Competent BMCs Is Associated With a Decrease in Natriuretic Peptide Serum Levels and Improved Survival of Patients With Chronic Postinfarction Heart Failure: Results of the TOPCARE-CHD Registry Circ. Res., April 27, 2007; 100(8): 1234 - 1241. [Abstract] [Full Text] [PDF]
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D. Perera, G. S. Kanaganayagam, M. Saha, R. Rashid, M. S. Marber, and S. R. Redwood Coronary Collaterals Remain Recruitable After Percutaneous Intervention Circulation, April 17, 2007; 115(15): 2015 - 2021. [Abstract] [Full Text] [PDF]
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X.-X. Wang, F.-R. Zhang, Y.-P. Shang, J.-H. Zhu, X.-D. Xie, Q.-M. Tao, J.-H. Zhu, and J.-Z. Chen Transplantation of Autologous Endothelial Progenitor Cells May Be Beneficial in Patients With Idiopathic Pulmonary Arterial Hypertension: A Pilot Randomized Controlled Trial J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1566 - 1571. [Abstract] [Full Text] [PDF]
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S. L.M.A. Beeres, F. M. Bengel, J. Bartunek, D. E. Atsma, J. M. Hill, M. Vanderheyden, M. Penicka, M. J. Schalij, W. Wijns, and J. J. Bax Role of Imaging in Cardiac Stem Cell Therapy J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1137 - 1148. [Abstract] [Full Text] [PDF]
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S. Vandervelde, M. J.A. van Luyn, M. H. Rozenbaum, A. H. Petersen, R. A. Tio, and M. C. Harmsen Stem cell-related cardiac gene expression early after murine myocardial infarction Cardiovasc Res, March 1, 2007; 73(4): 783 - 793. [Abstract] [Full Text] [PDF]
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S. Kasama, T. Toyama, T. Hatori, H. Sumino, H. Kumakura, Y. Takayama, S. Ichikawa, T. Suzuki, and M. Kurabayashi Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients With First Anterior Acute Myocardial Infarction J. Am. Coll. Cardiol., February 13, 2007; 49(6): 667 - 674. [Abstract] [Full Text] [PDF]
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E. Chavakis, A. Hain, M. Vinci, G. Carmona, M. E. Bianchi, P. Vajkoczy, A. M. Zeiher, T. Chavakis, and S. Dimmeler High-Mobility Group Box 1 Activates Integrin-Dependent Homing of Endothelial Progenitor Cells Circ. Res., February 2, 2007; 100(2): 204 - 212. [Abstract] [Full Text] [PDF]
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S. Zhu, X. Liu, Y. Li, P. J. Goldschmidt-Clermont, and C. Dong Aging in the Atherosclerosis Milieu May Accelerate the Consumption of Bone Marrow Endothelial Progenitor Cells Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 113 - 119. [Abstract] [Full Text] [PDF]
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A. Aicher, C. Heeschen, K.-i. Sasaki, C. Urbich, A. M. Zeiher, and S. Dimmeler Low-Energy Shock Wave for Enhancing Recruitment of Endothelial Progenitor Cells: A New Modality to Increase Efficacy of Cell Therapy in Chronic Hind Limb Ischemia Circulation, December 19, 2006; 114(25): 2823 - 2830. [Abstract] [Full Text] [PDF]
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M Saha, R Zbinden, S R Redwood, and M S Marber Stem cells to repair the broken heart: much ado about nothing? Heart, December 1, 2006; 92(12): 1717 - 1719. [Abstract] [Full Text] [PDF]
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L. C. Amado, K. H. Schuleri, A. P. Saliaris, A. J. Boyle, R. Helm, B. Oskouei, M. Centola, V. Eneboe, R. Young, J. A.C. Lima, et al. Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2116 - 2124. [Abstract] [Full Text] [PDF]
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R. Zhou, P. D. Acton, and V. A. Ferrari Imaging Stem Cells Implanted in Infarcted Myocardium J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2094 - 2106. [Abstract] [Full Text] [PDF]
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A. Kawamoto, H. Iwasaki, K. Kusano, T. Murayama, A. Oyamada, M. Silver, C. Hulbert, M. Gavin, A. Hanley, H. Ma, et al. CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells Circulation, November 14, 2006; 114(20): 2163 - 2169. [Abstract] [Full Text] [PDF]
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