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(Circulation. 2001;103:634.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
From the Division of Cardiovascular Research, St Elizabeths Medical Center, Tufts University School of Medicine, Boston, Mass.
Correspondence to Takayuki Asahara, MD, or Jeffrey M. Isner, MD, St Elizabeths Medical Center, 736 Cambridge Street, Boston, MA 02135. E-mail VeJeff{at}aol.com
BackgroundWe investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization.
Methods and ResultsPeripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 106 EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 106 EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells.
ConclusionsEx vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.
Key Words: endothelium stem cells ischemia regeneration neovascularization
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N. Werner, S. Kosiol, T. Schiegl, P. Ahlers, K. Walenta, A. Link, M. Bohm, and G. Nickenig Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes N. Engl. J. Med., September 8, 2005; 353(10): 999 - 1007. [Abstract] [Full Text] [PDF] |
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C. Kupatt, R. Hinkel, M. Lamparter, M.-L. von Bruhl, T. Pohl, J. Horstkotte, H. Beck, S. Muller, S. Delker, F.-J. Gildehaus, et al. Retroinfusion of Embryonic Endothelial Progenitor Cells Attenuates Ischemia-Reperfusion Injury in Pigs: Role of Phosphatidylinositol 3-Kinase/AKT Kinase Circulation, August 30, 2005; 112(9_suppl): I-117 - I-122. [Abstract] [Full Text] [PDF] |
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M. Siepe, C. Heilmann, P. von Samson, P. Menasche, and F. Beyersdorf Stem cell research and cell transplantation for myocardial regeneration Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 318 - 324. [Abstract] [Full Text] [PDF] |
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S. Murasawa, A. Kawamoto, M. Horii, S. Nakamori, and T. Asahara Niche-Dependent Translineage Commitment of Endothelial Progenitor Cells, Not Cell Fusion in General, Into Myocardial Lineage Cells Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1388 - 1394. [Abstract] [Full Text] [PDF] |
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V. J. Dzau, M. Gnecchi, A. S. Pachori, F. Morello, and L. G. Melo Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases Hypertension, July 1, 2005; 46(1): 7 - 18. [Abstract] [Full Text] [PDF] |
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N. Nagaya, H. Mori, S. Murakami, K. Kangawa, and S. Kitamura Adrenomedullin: angiogenesis and gene therapy Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1432 - R1437. [Abstract] [Full Text] [PDF] |
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U. Landmesser, F. Bahlmann, M. Mueller, S. Spiekermann, N. Kirchhoff, S. Schulz, C. Manes, D. Fischer, K. de Groot, D. Fliser, et al. Simvastatin Versus Ezetimibe: Pleiotropic and Lipid-Lowering Effects on Endothelial Function in Humans Circulation, May 10, 2005; 111(18): 2356 - 2363. [Abstract] [Full Text] [PDF] |
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M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF] |
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D. Schmidt, A. Mol, S. Neuenschwander, C. Breymann, M. Gossi, G. Zund, M. Turina, and S. P. Hoerstrup Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 795 - 800. [Abstract] [Full Text] [PDF] |
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P. Madeddu Therapeutic angiogenesis and vasculogenesis for tissue regeneration Exp Physiol, May 1, 2005; 90(3): 315 - 326. [Abstract] [Full Text] [PDF] |
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D. A. Ingram, L. E. Mead, D. B. Moore, W. Woodard, A. Fenoglio, and M. C. Yoder Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells Blood, April 1, 2005; 105(7): 2783 - 2786. [Abstract] [Full Text] [PDF] |
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M. Ii, H. Nishimura, A. Iwakura, A. Wecker, E. Eaton, T. Asahara, and D. W. Losordo Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via "Imported" Nitric Oxide Synthase Activity Circulation, March 8, 2005; 111(9): 1114 - 1120. [Abstract] [Full Text] [PDF] |
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J. Sugawara, M. Mitsui-Saito, T. Hoshiai, C. Hayashi, Y. Kimura, and K. Okamura Circulating Endothelial Progenitor Cells during Human Pregnancy J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1845 - 1848. [Abstract] [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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S. Murasawa and T. Asahara Endothelial Progenitor Cells for Vasculogenesis Physiology, February 1, 2005; 20(1): 36 - 42. [Abstract] [Full Text] [PDF] |
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M. S. Goligorsky Whispers and shouts in the pathogenesis of acute renal ischaemia Nephrol. Dial. Transplant., February 1, 2005; 20(2): 261 - 266. [Full Text] [PDF] |
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B. Dawn and R. Bolli Bone marrow cells for cardiac regeneration: the quest for the protagonist continues Cardiovasc Res, February 1, 2005; 65(2): 293 - 295. [Full Text] [PDF] |
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S. Davani, F. Deschaseaux, D. Chalmers, P. Tiberghien, and J.-P. Kantelip Can stem cells mend a broken heart? Cardiovasc Res, February 1, 2005; 65(2): 305 - 316. [Abstract] [Full Text] [PDF] |
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O. M. Tepper, J. M. Capla, R. D. Galiano, D. J. Ceradini, M. J. Callaghan, M. E. Kleinman, and G. C. Gurtner Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow-derived cells Blood, February 1, 2005; 105(3): 1068 - 1077. [Abstract] [Full Text] [PDF] |
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E. Chavakis, A. Aicher, C. Heeschen, K.-i. Sasaki, R. Kaiser, N. El Makhfi, C. Urbich, T. Peters, K. Scharffetter-Kochanek, A. M. Zeiher, et al. Role of {beta}2-integrins for homing and neovascularization capacity of endothelial progenitor cells J. Exp. Med., January 3, 2005; 201(1): 63 - 72. [Abstract] [Full Text] [PDF] |
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N. Sengupta, S. Caballero, R. N. Mames, A. M. Timmers, D. Saban, and M. B. Grant Preventing Stem Cell Incorporation into Choroidal Neovascularization by Targeting Homing and Attachment Factors Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 343 - 348. [Abstract] [Full Text] [PDF] |
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U. Ghani, A. Shuaib, A. Salam, A. Nasir, U. Shuaib, T. Jeerakathil, F. Sher, F. O'Rourke, A. M. Nasser, B. Schwindt, et al. Endothelial Progenitor Cells During Cerebrovascular Disease Stroke, January 1, 2005; 36(1): 151 - 153. [Abstract] [Full Text] [PDF] |
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D. Fliser, K. de Groot, F. H. Bahlmann, and H. Haller Cardiovascular disease in renal patients--a matter of stem cells? Nephrol. Dial. Transplant., December 1, 2004; 19(12): 2952 - 2954. [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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