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Circulation Research. 2004;95:343-353
doi: 10.1161/01.RES.0000137877.89448.78
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(Circulation Research. 2004;95:343.)
© 2004 American Heart Association, Inc.


Reviews

Endothelial Progenitor Cells

Characterization and Role in Vascular Biology

Carmen Urbich, Stefanie Dimmeler

From Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany.

Correspondence to Stefanie Dimmeler, PhD, Molecular Cardiology, Dept of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Dimmeler{at}em.uni-frankfurt.de

This Review is part of a thematic series on Angiogenesis, which includes the following articles:

Endothelial Progenitor Cells: Characterization and Role in Vascular Biology

Bone Marrow–Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences

Arteriogenesis

Innate Immunity and Angiogenesis

Syndecans

Growth Factors and Blood Vessels: Differentiation and Maturation
Ralph Kelly Guest Editor

Infusion of different hematopoietic stem cell populations and ex vivo expanded endothelial progenitor cells augments neovascularization of tissue after ischemia and contributes to reendothelialization after endothelial injury, thereby, providing a novel therapeutic option. However, controversy exists with respect to the identification and the origin of endothelial progenitor cells. Overall, there is consensus that endothelial progenitor cells can derive from the bone marrow and that CD133/VEGFR2 cells represent a population with endothelial progenitor capacity. However, increasing evidence suggests that there are additional bone marrow-derived cell populations (eg, myeloid cells, "side population" cells, and mesenchymal cells) and non-bone marrow-derived cells, which also can give rise to endothelial cells. The characterization of the different progenitor cell populations and their functional properties are discussed. Mobilization and endothelial progenitor cell-mediated neovascularization is critically regulated. Stimulatory (eg, statins and exercise) or inhibitory factors (risk factors for coronary artery disease) modulate progenitor cell levels and, thereby, affect the vascular repair capacity. Moreover, recruitment and incorporation of endothelial progenitor cells requires a coordinated sequence of multistep adhesive and signaling events including adhesion and migration (eg, by integrins), chemoattraction (eg, by SDF-1/CXCR4), and finally the differentiation to endothelial cells. This review summarizes the mechanisms regulating endothelial progenitor cell-mediated neovascularization and reendothelialization.


Key Words: progenitor cells • neovascularization • vasculogenesis • angiogenesis • endothelial cells




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CirculationHome page
K. Stellos, H. Langer, K. Daub, T. Schoenberger, A. Gauss, T. Geisler, B. Bigalke, I. Mueller, M. Schumm, I. Schaefer, et al.
Platelet-Derived Stromal Cell-Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34+ Cells to Endothelial Progenitor Cells
Circulation, January 15, 2008; 117(2): 206 - 215.
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Arterioscler. Thromb. Vasc. Bio.Home page
P. Madeddu, N. Kraenkel, L. S. Barcelos, M. Siragusa, P. Campagnolo, A. Oikawa, A. Caporali, A. Herman, O. Azzolino, L. Barberis, et al.
Phosphoinositide 3-Kinase {gamma} Gene Knockout Impairs Postischemic Neovascularization and Endothelial Progenitor Cell Functions
Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 68 - 76.
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Hum ReprodHome page
M. Mints, M. Jansson, B. Sadeghi, M. Westgren, M. Uzunel, M. Hassan, and J. Palmblad
Endometrial endothelial cells are derived from donor stem cells in a bone marrow transplant recipient
Hum. Reprod., January 1, 2008; 23(1): 139 - 143.
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HeartHome page
W Wojakowski, M Kucia, M Kazmierski, M Z Ratajczak, and M Tendera
Circulating progenitor cells in stable coronary heart disease and acute coronary syndromes: relevant reparatory mechanism?
Heart, January 1, 2008; 94(1): 27 - 33.
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Exp PhysiolHome page
M. T. Kearney, E. R. Duncan, M. Kahn, and S. B. Wheatcroft
Insulin resistance and endothelial cell dysfunction: studies in mammalian models
Exp Physiol, January 1, 2008; 93(1): 158 - 163.
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Circ. Res.Home page
M. Koyanagi, P. Bushoven, M. Iwasaki, C. Urbich, A. M. Zeiher, and S. Dimmeler
Notch Signaling Contributes to the Expression of Cardiac Markers in Human Circulating Progenitor Cells
Circ. Res., November 26, 2007; 101(11): 1139 - 1145.
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J. Thorac. Cardiovasc. Surg.Home page
E. J. Suuronen, J. Price, J. P. Veinot, K. Ascah, V. Kapila, X.-W. Guo, S. Wong, T. G. Mesana, and M. Ruel
Comparative effects of mesenchymal progenitor cells, endothelial progenitor cells, or their combination on myocardial infarct regeneration and cardiac function.
J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1249 - 1258.
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Arterioscler. Thromb. Vasc. Bio.Home page
M. Y.K. Lee, H.-F. Tse, C.-W. Siu, S.-G. Zhu, R. Y.K. Man, and P. M. Vanhoutte
Genomic Changes in Regenerated Porcine Coronary Arterial Endothelial Cells
Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2443 - 2449.
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J. Am. Soc. Nephrol.Home page
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.
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Proc. Natl. Acad. Sci. USAHome page
J. M. L. Ebos, C. R. Lee, J. G. Christensen, A. J. Mutsaers, and R. S. Kerbel
Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy
PNAS, October 23, 2007; 104(43): 17069 - 17074.
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CirculationHome page
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.
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CirculationHome page
Z. Li, J. C. Wu, A. Y. Sheikh, D. Kraft, F. Cao, X. Xie, M. Patel, S. S. Gambhir, R. C. Robbins, J. P. Cooke, et al.
Differentiation, Survival, and Function of Embryonic Stem Cell Derived Endothelial Cells for Ischemic Heart Disease
Circulation, September 11, 2007; 116(11_suppl): I-46 - I-54.
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Arterioscler. Thromb. Vasc. Bio.Home page
B. Mees, S. Wagner, E. Ninci, S. Tribulova, S. Martin, R. van Haperen, S. Kostin, M. Heil, R. de Crom, and W. Schaper
Endothelial Nitric Oxide Synthase Activity Is Essential for Vasodilation During Blood Flow Recovery but not for Arteriogenesis
Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1926 - 1933.
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HeartHome page
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.
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Eur Heart JHome page
W. Wojakowski, M. Kazmierski, B. Korzeniowska, and M. Tendera
Link between erythropoietin release and mobilization of endothelial progenitor cells in acute myocardial infarction
Eur. Heart J., August 1, 2007; 28(15): 1785 - 1786.
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Eur J Heart FailHome page
H.-F. Tse, C.-W. Siu, S.-G. Zhu, L. Songyan, Q.-Y. Zhang, W.-H. Lai, Y.-L. Kwong, J. Nicholls, and C.-P. Lau
Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium
Eur J Heart Fail, August 1, 2007; 9(8): 747 - 753.
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BloodHome page
S. Levenberg, J. Zoldan, Y. Basevitch, and R. Langer
Endothelial potential of human embryonic stem cells
Blood, August 1, 2007; 110(3): 806 - 814.
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Ann Rheum DisHome page
P. E Westerweel, R. K M A C Luijten, I. E Hoefer, H. A Koomans, R. H W M Derksen, and M. C Verhaar
Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus
Ann Rheum Dis, July 1, 2007; 66(7): 865 - 870.
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BloodHome page
M. Nagano, T. Yamashita, H. Hamada, K. Ohneda, K.-i. Kimura, T. Nakagawa, M. Shibuya, H. Yoshikawa, and O. Ohneda
Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood
Blood, July 1, 2007; 110(1): 151 - 160.
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Proc. Natl. Acad. Sci. USAHome page
K.-H. Chang, T. Chan-Ling, E. L. McFarland, A. Afzal, H. Pan, L. C. Baxter, L. C. Shaw, S. Caballero, N. Sengupta, S. L. Calzi, et al.
IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development
PNAS, June 19, 2007; 104(25): 10595 - 10600.
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Cancer Res.Home page
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.
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E. W. Raines
Inflamed endothelium: an EPC adhesion kit
Blood, May 15, 2007; 109(10): 4118 - 4118.
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R. R. Langley and I. J. Fidler
Tumor Cell-Organ Microenvironment Interactions in the Pathogenesis of Cancer Metastasis
Endocr. Rev., May 1, 2007; 28(3): 297 - 321.
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Diabetes CareHome page
G. P. Fadini, S. Sartore, C. Agostini, and A. Avogaro
Significance of Endothelial Progenitor Cells in Subjects With Diabetes
Diabetes Care, May 1, 2007; 30(5): 1305 - 1313.
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Arterioscler. Thromb. Vasc. Bio.Home page
T. Thum, D. Fraccarollo, S. Thum, M. Schultheiss, A. Daiber, P. Wenzel, T. Munzel, G. Ertl, and J. Bauersachs
Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress
Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 748 - 754.
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Arterioscler. Thromb. Vasc. Bio.Home page
C. Murphy, G. S. Kanaganayagam, B. Jiang, P. J. Chowienczyk, R. Zbinden, M. Saha, S. Rahman, A. M. Shah, M. S. Marber, and M. T. Kearney
Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men
Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 936 - 942.
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