on November 11, 2002
Circulation. 2002
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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© 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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C. Valina, K. Pinkernell, Y.-H. Song, X. Bai, S. Sadat, R. J. Campeau, T. H. Le Jemtel, and E. Alt Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction Eur. Heart J., November 1, 2007; 28(21): 2667 - 2677. [Abstract] [Full Text] [PDF]
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M. J. Lipinski, G. G.L. Biondi-Zoccai, A. Abbate, R. Khianey, I. Sheiban, J. Bartunek, M. Vanderheyden, H.-S. Kim, H.-J. Kang, B. E. Strauer, et al. Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction: A Collaborative Systematic Review and Meta-Analysis of Controlled Clinical Trials J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1761 - 1767. [Abstract] [Full Text] [PDF]
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J. Hur, H.-M. Yang, C.-H. Yoon, C.-S. Lee, K.-W. Park, J.-H. Kim, T.-Y. Kim, J.-Y. Kim, H.-J. Kang, I.-H. Chae, et al. Identification of a Novel Role of T Cells in Postnatal Vasculogenesis: Characterization of Endothelial Progenitor Cell Colonies Circulation, October 9, 2007; 116(15): 1671 - 1682. [Abstract] [Full Text] [PDF]
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M. Zhang, N. Mal, M. Kiedrowski, M. Chacko, A. T. Askari, Z. B. Popovic, O. N. Koc, and M. S. Penn SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction FASEB J, October 1, 2007; 21(12): 3197 - 3207. [Abstract] [Full Text] [PDF]
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T. Sobrino, O. Hurtado, M. A. Moro, M. Rodriguez-Yanez, M. Castellanos, D. Brea, O. Moldes, M. Blanco, J. F. Arenillas, R. Leira, et al. The Increase of Circulating Endothelial Progenitor Cells After Acute Ischemic Stroke Is Associated With Good Outcome Stroke, October 1, 2007; 38(10): 2759 - 2764. [Abstract] [Full Text] [PDF]
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J. Makela, K. Ylitalo, S. Lehtonen, S. Dahlbacka, E. Niemela, K. Kiviluoma, J. Rimpilainen, H. Alaoja, T. Paavonen, P. Lehenkari, et al. Bone marrow derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site J. Thorac. Cardiovasc. Surg., September 1, 2007; 134(3): 565 - 573. [Abstract] [Full Text] [PDF]
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H. Shmilovich, V. Deutsch, A. Roth, H. Miller, G. Keren, and J. George Circulating endothelial progenitor cells in patients with cardiac syndrome X Heart, September 1, 2007; 93(9): 1071 - 1076. [Abstract] [Full Text] [PDF]
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M. Breitbach, T. Bostani, W. Roell, Y. Xia, O. Dewald, J. M. Nygren, J. W. U. Fries, K. Tiemann, H. Bohlen, J. Hescheler, et al. Potential risks of bone marrow cell transplantation into infarcted hearts Blood, August 15, 2007; 110(4): 1362 - 1369. [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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