Circulation. 2003;108:2511-2516
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000096483.29777.50
Published online before print October 27, 2003, doi: 10.1161/01.CIR.0000096483.29777.50
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(Circulation. 2003;108:2511.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Relevance of Monocytic Features for Neovascularization Capacity of Circulating Endothelial Progenitor Cells
From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
Correspondence to Stefanie Dimmeler, PhD, Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de
Received April 15, 2003; de novo received July 3, 2003; revision received July 22, 2003; accepted July 22, 2003.
Background— Transplantation of ex vivo expanded circulating endothelial progenitor cells (EPCs) from peripheral blood mononuclear cells improves the neovascularization after critical ischemia. However, the origin of the endothelial progenitor lineage and its characteristics have not yet been clearly defined. Therefore, we investigated whether the phenotype and functional capacity of EPCs to improve neovascularization depend on their monocytic origin.
Methods and Results— Monocytic CD14+ cells were isolated from mononuclear cells and incubated on fibronectin-coated dishes in endothelial medium in the presence of vascular endothelial growth factor. After 4 days of cultivation, adherent cells deriving from CD14+ or CD14- mononuclear cells showed equal expression of endothelial marker proteins and capacity for clonal expansion as determined by measuring endothelial colony-forming units. In addition, transplanted EPCs (5x105 cells) deriving from CD14+ or CD14- cells were incorporated into vascular structures of nude mice after hind-limb ischemia and significantly improved neovascularization from 0.27±0.12 (no cells) to 0.66±0.12 and 0.65±0.17, respectively (P<0.001; laser Doppler-derived relative blood flow). In contrast, no functional improvement of neovascularization was detected when freshly isolated CD14+ mononuclear cells without ex vivo expansion were used (0.33±0.17). Moreover, macrophages or dendritic cells differentiated from isolated CD14+ cells were significantly less effective in improving neovascularization than EPCs cultivated from the same starting population (P<0.01).
Conclusions— These data demonstrate that EPCs can be generated from nonmonocytic CD14- peripheral blood mononuclear cells and exhibit a unique functional activity to improve neovascularization after hind-limb ischemia.
Key Words: angiogenesis • endothelium • cells
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 L. Rossig, C. Urbich, T. Bruhl, E. Dernbach, C. Heeschen, E. Chavakis, K.-i. Sasaki, D. Aicher, F. Diehl, F. Seeger, et al. Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells J. Exp. Med., June 6, 2005; 201(11): 1825 - 1835. [Abstract] [Full Text] [PDF]
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 A. M. Leone, S. Rutella, G. Bonanno, A. Abbate, A. G. Rebuzzi, S. Giovannini, M. Lombardi, L. Galiuto, G. Liuzzo, F. Andreotti, et al. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function Eur. Heart J., June 2, 2005; 26(12): 1196 - 1204. [Abstract] [Full Text] [PDF]
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B. Modarai, K.G. Burnand, B. Sawyer, and A. Smith Endothelial Progenitor Cells Are Recruited Into Resolving Venous Thrombi Circulation, May 24, 2005; 111(20): 2645 - 2653. [Abstract] [Full Text] [PDF]
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H. Uchimura, T. Marumo, O. Takase, H. Kawachi, F. Shimizu, M. Hayashi, T. Saruta, K. Hishikawa, and T. Fujita Intrarenal Injection of Bone Marrow-Derived Angiogenic Cells Reduces Endothelial Injury and Mesangial Cell Activation in Experimental Glomerulonephritis J. Am. Soc. Nephrol., April 1, 2005; 16(4): 997 - 1004. [Abstract] [Full Text] [PDF]
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F. H. Bahlmann, K. de Groot, O. Mueller, B. Hertel, H. Haller, and D. Fliser Stimulation of Endothelial Progenitor Cells: A New Putative Therapeutic Effect of Angiotensin II Receptor Antagonists Hypertension, April 1, 2005; 45(4): 526 - 529. [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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A. Aicher, A. M. Zeiher, and S. Dimmeler Mobilizing Endothelial Progenitor Cells Hypertension, March 1, 2005; 45(3): 321 - 325. [Abstract] [Full Text] [PDF]
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T. M. Powell, J. D. Paul, J. M. Hill, M. Thompson, M. Benjamin, M. Rodrigo, J. P. McCoy, E. J. Read, H. M. Khuu, S. F. Leitman, et al. Granulocyte Colony-Stimulating Factor Mobilizes Functional Endothelial Progenitor Cells in Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 296 - 301. [Abstract] [Full Text] [PDF]
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J. R. Conejo-Garcia, R. J. Buckanovich, F. Benencia, M. C. Courreges, S. C. Rubin, R. G. Carroll, and G. Coukos Vascular leukocytes contribute to tumor vascularization Blood, January 15, 2005; 105(2): 679 - 681. [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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G. Nowak, A. Karrar, C. Holmen, S. Nava, M. Uzunel, K. Hultenby, and S. Sumitran-Holgersson Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization Circulation, December 14, 2004; 110(24): 3699 - 3707. [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. De Falco, D. Porcelli, A. R. Torella, S. Straino, M. G. Iachininoto, A. Orlandi, S. Truffa, P. Biglioli, M. Napolitano, M. C. Capogrossi, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells Blood, December 1, 2004; 104(12): 3472 - 3482. [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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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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I. Rajantie, M. Ilmonen, A. Alminaite, U. Ozerdem, K. Alitalo, and P. Salven Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells Blood, October 1, 2004; 104(7): 2084 - 2086. [Abstract] [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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K. L. March and B. H. Johnstone Cellular approaches to tissue repair in cardiovascular disease: the more we know, the more there is to learn Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H458 - H463. [Full Text] [PDF]
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T. Kondo, M. Hayashi, K. Takeshita, Y. Numaguchi, K. Kobayashi, S. Iino, Y. Inden, and T. Murohara Smoking Cessation Rapidly Increases Circulating Progenitor Cells in Peripheral Blood in Chronic Smokers Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1442 - 1447. [Abstract] [Full Text] [PDF]
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J. Honold, B. Assmus, R. Lehman, A. M. Zeiher, and S. Dimmeler Stem cell therapy of cardiac disease: an update Nephrol. Dial. Transplant., July 1, 2004; 19(7): 1673 - 1677. [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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