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
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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
This article has been cited by other articles:
 |
|
 |
|
  C.-F. Lam, P.-J. Chang, Y.-S. Huang, Y.-H. Sung, C.-C. Huang, M.-W. Lin, Y.-C. Liu, and Y.-C. Tsai Prolonged Use of High-Dose Morphine Impairs Angiogenesis and Mobilization of Endothelial Progenitor Cells in Mice Anesth. Analg., August 1, 2008; 107(2): 686 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. He, T. Lu, L. V. d'Uscio, C.-F. Lam, H.-C. Lee, and Z. S. Katusic Angiogenic Function of Prostacyclin Biosynthesis in Human Endothelial Progenitor Cells Circ. Res., July 3, 2008; 103(1): 80 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. de Silva, A. N. Raval, M. Hadi, K. M. Gildea, A. C. Bonifacino, Z.-X. Yu, Y. Y. Yau, S. F. Leitman, S. L. Bacharach, R. E. Donahue, et al. Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction Eur. Heart J., July 2, 2008; 29(14): 1772 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P.W. Rouhl, R. J. van Oostenbrugge, J. Damoiseaux, J.-W. C. Tervaert, and J. Lodder Endothelial Progenitor Cell Research in Stroke: A Potential Shift in Pathophysiological and Therapeutical Concepts Stroke, July 1, 2008; 39(7): 2158 - 2165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Pedrotty, R. Y. Klinger, N. Badie, S. Hinds, A. Kardashian, and N. Bursac Structural coupling of cardiomyocytes and noncardiomyocytes: quantitative comparisons using a novel micropatterned cell pair assay Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H390 - H400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dimmeler and A. Leri Aging and Disease as Modifiers of Efficacy of Cell Therapy Circ. Res., June 6, 2008; 102(11): 1319 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Martin-Rendon, S. J. Brunskill, C. J. Hyde, S. J. Stanworth, A. Mathur, and S. M. Watt Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review Eur. Heart J., June 3, 2008; (2008) ehn220v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Yang, H.-Y. Qian, J. Huang, Y.-J. Geng, R.-L. Gao, K.-F. Dou, G.-S. Yang, J.-J. Li, R. Shen, Z.-X. He, et al. Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts Eur. Heart J., June 2, 2008; 29(12): 1578 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kasama, M. Furuya, T. Toyama, S. Ichikawa, and M. Kurabayashi Effect of atrial natriuretic peptide on left ventricular remodelling in patients with acute myocardial infarction Eur. Heart J., June 2, 2008; 29(12): 1485 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mifune, T. Matsumoto, A. Kawamoto, R. Kuroda, T. Shoji, H. Iwasaki, S.-M. Kwon, M. Miwa, M. Kurosaka, and T. Asahara Local Delivery of Granulocyte Colony Stimulating Factor-Mobilized CD34-Positive Progenitor Cells Using Bioscaffold for Modality of Unhealing Bone Fracture Stem Cells, June 1, 2008; 26(6): 1395 - 1405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Kalka and I. Baumgartner Gene and stem cell therapy in peripheral arterial occlusive disease Vascular Medicine, May 1, 2008; 13(2): 157 - 172. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Tayyareci, M. Sezer, B. Umman, S. Besisik, A. Mudun, Y. Sanli, A. Oncul, N. Gurses, D. Sargin, M. Meric, et al. Intracoronary Autologous Bone Marrow-Derived Mononuclear Cell Transplantation Improves Coronary Collateral Vessel Formation and Recruitment Capacity in Patients With Ischemic Cardiomyopathy: A Combined Hemodynamic and Scintigraphic Approach Angiology, May 1, 2008; 59(2): 145 - 155. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions Cardiovasc Res, May 1, 2008; 78(2): 257 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Chavakis, G. Carmona, C. Urbich, S. Gottig, R. Henschler, J. M. Penninger, A. M. Zeiher, T. Chavakis, and S. Dimmeler Phosphatidylinositol-3-Kinase-{gamma} Is Integral to Homing Functions of Progenitor Cells Circ. Res., April 25, 2008; 102(8): 942 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tei, T. Matsumoto, Y. Mifune, K. Ishida, K. Sasaki, T. Shoji, S. Kubo, A. Kawamoto, T. Asahara, M. Kurosaka, et al. Administrations of Peripheral Blood CD34-Positive Cells Contribute to Medial Collateral Ligament Healing via Vasculogenesis Stem Cells, March 1, 2008; 26(3): 819 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Carmona, E. Chavakis, U. Koehl, A. M. Zeiher, and S. Dimmeler Activation of Epac stimulates integrin-dependent homing of progenitor cells Blood, March 1, 2008; 111(5): 2640 - 2646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Burt, Y. Loh, W. Pearce, N. Beohar, W. G. Barr, R. Craig, Y. Wen, J. A. Rapp, and J. Kessler Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases JAMA, February 27, 2008; 299(8): 925 - 936. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Sieveking, A. Buckle, D. S. Celermajer, and M. K.C. Ng Strikingly different angiogenic properties of endothelial progenitor cell subpopulations: insights from a novel human angiogenesis assay. J. Am. Coll. Cardiol., February 12, 2008; 51(6): 660 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Atluri, C. M. Panlilio, G. P. Liao, E. E. Suarez, R. C. McCormick, W. Hiesinger, J. E. Cohen, M. J. Smith, A. B. Patel, W. Feng, et al. Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dimmeler, J. Burchfield, and A. M. Zeiher Cell-Based Therapy of Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. O. Traktuev, S. Merfeld-Clauss, J. Li, M. Kolonin, W. Arap, R. Pasqualini, B. H. Johnstone, and K. L. March A Population of Multipotent CD34-Positive Adipose Stromal Cells Share Pericyte and Mesenchymal Surface Markers, Reside in a Periendothelial Location, and Stabilize Endothelial Networks Circ. Res., January 4, 2008; 102(1): 77 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Horvath and Y. Zhou Transmyocardial Laser Revascularization and Extravascular Angiogenetic Techniques to Increase Myocardial Blood Flow Card. Surg. Adult, January 1, 2008; 3(2008): 733 - 752. [Full Text]
|
|
|
|
|
|
R. P. Gallegos and R. M. Bolman III Stem Cell Induced Regeneration of Myocardium Card. Surg. Adult, January 1, 2008; 3(2008): 1657 - 1668. [Full Text]
|
|
|
|
 |
|
 Y. Suarez, B. R. Shepherd, D. A. Rao, and J. S. Pober Alloimmunity to Human Endothelial Cells Derived from Cord Blood Progenitors J. Immunol., December 1, 2007; 179(11): 7488 - 7496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Fotuhi, Y.-H. Song, and E. Alt Electrophysiological consequence of adipose-derived stem cell transplantation in infarcted porcine myocardium Europace, December 1, 2007; 9(12): 1218 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kanayasu-Toyoda, A. Ishii-Watabe, T. Suzuki, T. Oshizawa, and T. Yamaguchi A New Role of Thrombopoietin Enhancing ex Vivo Expansion of Endothelial Precursor Cells Derived from AC133-positive Cells J. Biol. Chem., November 16, 2007; 282(46): 33507 - 33514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 J. Tongers and D. W. Losordo Frontiers in Nephrology: The Evolving Therapeutic Applications of Endothelial Progenitor Cells J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2843 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 B. Doyle, B. J. Kemp, P. Chareonthaitawee, C. Reed, J. Schmeckpeper, P. Sorajja, S. Russell, P. Araoz, S. J. Riederer, and N. M. Caplice Dynamic Tracking During Intracoronary Injection of 18F-FDG-Labeled Progenitor Cell Therapy for Acute Myocardial Infarction J. Nucl. Med., October 1, 2007; 48(10): 1708 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
D. Simpson, H. Liu, T.-H. M. Fan, R. Nerem, and S. C. Dudley Jr. A Tissue Engineering Approach to Progenitor Cell Delivery Results in Significant Cell Engraftment and Improved Myocardial Remodeling Stem Cells, September 1, 2007; 25(9): 2350 - 2357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
W. Li, N. Ma, L.-L. Ong, C. Nesselmann, C. Klopsch, Y. Ladilov, D. Furlani, C. Piechaczek, J. M. Moebius, K. Lutzow, et al. Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function Stem Cells, August 1, 2007; 25(8): 2118 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nishiyama, S. Miyoshi, N. Hida, T. Uyama, K. Okamoto, Y. Ikegami, K. Miyado, K. Segawa, M. Terai, M. Sakamoto, et al. The Significant Cardiomyogenic Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells In Vitro Stem Cells, August 1, 2007; 25(8): 2017 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Wu, F. M. Bengel, and S. S. Gambhir Cardiovascular Molecular Imaging Radiology, August 1, 2007; 244(2): 337 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. M. Vartanian and R. Sarkar Therapeutic Angiogenesis Vascular and Endovascular Surgery, July 1, 2007; 41(3): 173 - 185. [Abstract] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 H.-F. Tse and C.-P. Lau Therapeutic Angiogenesis With Bone Marrow--Derived Stem Cells Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 89 - 97. [Abstract] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H.-K. Oh, J.-M. Ha, E. O, B. H. Lee, S. K. Lee, B.-S. Shim, Y.-K. Hong, and Y. A. Joe Tumor Angiogenesis Promoted by Ex vivo Differentiated Endothelial Progenitor Cells Is Effectively Inhibited by an Angiogenesis Inhibitor, TK1-2 Cancer Res., May 15, 2007; 67(10): 4851 - 4859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. S. Penn Patient and Cellular Characteristics Determine Efficacy of Cell Therapy Circ. Res., April 27, 2007; 100(8): 1101 - 1103. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|