Circulation. 2003;107:461-468
Published online before print December 30, 2002, doi: 10.1161/01.CIR.0000046450.89986.50
Published online before print December 30, 2002, doi: 10.1161/01.CIR.0000046450.89986.50
(Circulation. 2003;107:461.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Intramyocardial Transplantation of Autologous Endothelial Progenitor Cells for Therapeutic Neovascularization of Myocardial Ischemia
From the Division of Cardiovascular Research, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass (all authors), and the Department of Physiology, Tokai University School of Medicine, Japan (T.A.).
Correspondence to Takayuki Asahara, MD, or Douglas W. Losordo, MD, Division of Cardiovascular Research, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135. E-mail asa777{at}aol.com or douglas.losordo@tufts.edu
Background— We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia.
Methods and Results— Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31+ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31+ MNCs in noncoated plates, nonadhesive cells (NA/CD31+ MNCs) were harvested as the endothelial progenitor cell–enriched fraction. Nonadhesive CD31- cells (NA/CD31- MNCs) were also prepared. Autologous transplantation of 107 NA/CD31+ MNCs, 107 NA/CD31- MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 105 human CD34+ MNCs, 105 human CD34- MNCs, or PBS was transplanted into ischemic myocardium of nude rats 10 minutes after ligation of the left anterior descending coronary artery. In the swine study, ischemic area by NOGA mapping, Rentrop grade angiographic collateral development, and echocardiographic left ventricular ejection fraction improved significantly 4 weeks after transplantation of NA/CD31+ MNCs but not after injection of NA/CD31- MNCs or PBS. Capillary density in ischemic myocardium 4 weeks after transplantation was significantly greater in the NA/CD31+ MNC group than the control groups. In the rat study, echocardiographic left ventricular systolic function and capillary density were significantly better preserved in the CD34+ MNC group than in the control groups 4 weeks after myocardial ischemia.
Conclusions— These favorable outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous CD34+ MNCs in the setting of chronic myocardial ischemia.
Key Words: transplantation • cells • catheters • ischemia • vasculogenesis
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S. Dimmeler and A. M. Zeiher Wanted! The best cell for cardiac regeneration J. Am. Coll. Cardiol., July 21, 2004; 44(2): 464 - 466. [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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L. G. Melo, A. S. Pachori, D. Kong, M. Gnecchi, K. Wang, R. E. Pratt, and V. J. Dzau Molecular and Cell-Based Therapies for Protection, Rescue, and Repair of Ischemic Myocardium: Reasons for Cautious Optimism Circulation, May 25, 2004; 109(20): 2386 - 2393. [Full Text] [PDF]
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V. Adams, K. Lenk, A. Linke, D. Lenz, S. Erbs, M. Sandri, A. Tarnok, S. Gielen, F. Emmrich, G. Schuler, et al. Increase of Circulating Endothelial Progenitor Cells in Patients with Coronary Artery Disease After Exercise-Induced Ischemia Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 684 - 690. [Abstract] [Full Text] [PDF]
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J. C. Chachques, C. Acar, J. Herreros, J. C. Trainini, F. Prosper, N. D'Attellis, J.-N. Fabiani, and A. F. Carpentier Cellular cardiomyoplasty: clinical application Ann. Thorac. Surg., March 1, 2004; 77(3): 1121 - 1130. [Abstract] [Full Text] [PDF]
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M Fujita and K Tambara Recent insights into human coronary collateral development Heart, March 1, 2004; 90(3): 246 - 250. [Abstract] [Full Text] [PDF]
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P D Lambiase and M S Marber Myocardial gene and cell delivery Heart, January 1, 2004; 90(1): 1 - 2. [Abstract] [Full Text] [PDF]
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R. J. Scheubel, H. Zorn, R.-E. Silber, O. Kuss, H. Morawietz, J. Holtz, and A. Simm Age-dependent depression in circulating endothelial progenitor cells inpatients undergoing coronary artery bypass grafting J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2073 - 2080. [Abstract] [Full Text] [PDF]
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J. Herreros, F. Prosper, A. Perez, J. J Gavira, M. J. Garcia-Velloso, J. Barba, P. L Sanchez, C. Canizo, G. Rabago, J. M Marti-Climent, et al. Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction Eur. Heart J., November 2, 2003; 24(22): 2012 - 2020. [Abstract] [Full Text] [PDF]
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E. T.H. Yeh, S. Zhang, H. D. Wu, M. Korbling, J. T. Willerson, and Z. Estrov Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo Circulation, October 28, 2003; 108(17): 2070 - 2073. [Abstract] [Full Text] [PDF]
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N. Werner, S. Junk, U. Laufs, A. Link, K. Walenta, M. Bohm, and G. Nickenig Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury Circ. Res., July 25, 2003; 93 (2): e17 - e24. [Abstract] [Full Text] [PDF]
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