Circulation. 2003;108:2212-2218
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000095788.78169.AF
Published online before print October 13, 2003, doi: 10.1161/01.CIR.0000095788.78169.AF
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(Circulation. 2003;108:2212.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Infarct Remodeling After Intracoronary Progenitor Cell Treatment in Patients With Acute Myocardial Infarction (TOPCARE-AMI)
Mechanistic Insights From Serial Contrast-Enhanced Magnetic Resonance Imaging
From the Departments of Cardiology (M.B.B., B.A., R.L., J.H., V.S., S.D., A.M.Z.), Diagnostic and Interventional Radiology (N.D.A., J.S., T.J.V.), and Hematology (H.M.), J.W. Goethe-University Frankfurt, Frankfurt, Germany.
Correspondence to Stefanie Dimmeler, PhD, or Andreas M. Zeiher, MD, Department of Internal Medicine IV, J.W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de or zeiher@em.uni-frankfurt.de
Received May 7, 2003; de novo received June 30, 2003; revision received August 8, 2003; accepted August 13, 2003.
Background— Experimental and initial clinical studies suggest that transplantation of circulating blood– (CPC) or bone marrow–derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion.
Methods and Results— In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7±1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44±10% to 49±10%; P=0.003), a decrease in end-systolic volume (from 69±26 to 60±28 mL; P=0.003), and unchanged end-diastolic volumes (122±34 versus 117±37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46±32 to 37±28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling.
Conclusions— Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.
Key Words: cells • myocardial infarction • magnetic resonance imaging • remodeling
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C. Heiss, S. Keymel, U. Niesler, J. Ziemann, M. Kelm, and C. Kalka Impaired Progenitor Cell Activity in Age-Related Endothelial Dysfunction J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1441 - 1448. [Abstract] [Full Text] [PDF]
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P. L Weissberg and A. Qasim Stem cell therapy for myocardial repair Heart, May 1, 2005; 91(5): 696 - 702. [Full Text] [PDF]
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B. Dawn, A. B. Stein, K. Urbanek, M. Rota, B. Whang, R. Rastaldo, D. Torella, X.-L. Tang, A. Rezazadeh, J. Kajstura, et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function PNAS, March 8, 2005; 102(10): 3766 - 3771. [Abstract] [Full Text] [PDF]
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C. M. Kramer The prognostic significance of microvascular obstruction after myocardial infarction as defined by cardiovascular magnetic resonance Eur. Heart J., March 2, 2005; 26(6): 532 - 533. [Full Text] [PDF]
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V. Schachinger and A. M. Zeiher Stem Cells and Cardiovascular and Renal Disease: Today and Tomorrow J. Am. Soc. Nephrol., March 1, 2005; 16(3_suppl_1): S2 - S6. [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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M. Massa, V. Rosti, M. Ferrario, R. Campanelli, I. Ramajoli, R. Rosso, G. M. De Ferrari, M. Ferlini, L. Goffredo, A. Bertoletti, et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction Blood, January 1, 2005; 105(1): 199 - 206. [Abstract] [Full Text] [PDF]
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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]
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E. Dernbach, C. Urbich, R. P. Brandes, W. K. Hofmann, A. M. Zeiher, and S. Dimmeler Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress Blood, December 1, 2004; 104(12): 3591 - 3597. [Abstract] [Full Text] [PDF]
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J. V. Frangioni and R. J. Hajjar In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease Circulation, November 23, 2004; 110(21): 3378 - 3383. [Abstract] [Full Text] [PDF]
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I. Spyridopoulos, J. Haendeler, C. Urbich, T. H. Brummendorf, H. Oh, M. D. Schneider, A. M. Zeiher, and S. Dimmeler Statins Enhance Migratory Capacity by Upregulation of the Telomere Repeat-Binding Factor TRF2 in Endothelial Progenitor Cells Circulation, November 9, 2004; 110(19): 3136 - 3142. [Abstract] [Full Text] [PDF]
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L. Rossig, C. Urbich, and S. Dimmeler Endothelial Progenitor Cells at Work: Not Mature Yet, but Already Stress-Resistant Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1977 - 1979. [Full Text] [PDF]
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C. Weber, A. Schober, and A. Zernecke Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1997 - 2008. [Abstract] [Full Text] [PDF]
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V. Schachinger, B. Assmus, M. B. Britten, J. Honold, R. Lehmann, C. Teupe, N. D. Abolmaali, T. J. Vogl, W.-K. Hofmann, H. Martin, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one-year results of the TOPCARE-AMI Trial J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1690 - 1699. [Abstract] [Full Text] [PDF]
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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]
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M. Y. Flugelman and B. S. Lewis The promise of myocardial repair - towards a better understanding Eur. Heart J., September 1, 2004; 25(17): 1483 - 1485. [Full Text] [PDF]
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C. Urbich and S. Dimmeler Endothelial Progenitor Cells: Characterization and Role in Vascular Biology Circ. Res., August 20, 2004; 95(4): 343 - 353. [Abstract] [Full Text] [PDF]
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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]
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Y.-S. Yoon, J.-S. Park, T. Tkebuchava, C. Luedeman, and D. W. Losordo Unexpected Severe Calcification After Transplantation of Bone Marrow Cells in Acute Myocardial Infarction Circulation, June 29, 2004; 109(25): 3154 - 3157. [Abstract] [Full Text] [PDF]
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P. Anversa, M. A. Sussman, and R. Bolli Molecular Genetic Advances in Cardiovascular Medicine: Focus on the Myocyte Circulation, June 15, 2004; 109(23): 2832 - 2838. [Full Text] [PDF]
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D. W. Losordo and S. Dimmeler Therapeutic Angiogenesis and Vasculogenesis for Ischemic Disease: Part II: Cell-Based Therapies Circulation, June 8, 2004; 109(22): 2692 - 2697. [Full Text] [PDF]
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C. Heeschen, R. Lehmann, J. Honold, B. Assmus, A. Aicher, D. H. Walter, H. Martin, A. M. Zeiher, and S. Dimmeler Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease Circulation, April 6, 2004; 109(13): 1615 - 1622. [Abstract] [Full Text] [PDF]
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W. W. O'Neill and S. R. Dixon The year in interventional cardiology J. Am. Coll. Cardiol., March 3, 2004; 43(5): 875 - 890. [Full Text] [PDF]
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J. G.F. Cleland, N. Freemantle, G. Kaye, M. Nasir, P. Velavan, K. Lalukota, T. Mudawi, R. Shelton, A. L. Clark, and A. P. Coletta Clinical trials update from the American Heart Association meeting: {Omega}-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE Eur J Heart Fail, January 1, 2004; 6(1): 109 - 115. [Abstract] [Full Text] [PDF]
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