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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 952-958
Expression of VEGFR-2 and AC133 by circulating human
CD34+ cells identifies a population of functional
endothelial precursors
Mario Peichev,
Afzal J. Naiyer,
Daniel Pereira,
Zhenping Zhu,
William J. Lane,
Mathew Williams,
Mehmet C. Oz,
Daniel J. Hicklin,
Larry Witte,
Malcolm A. S. Moore, and
Shahin Rafii
From the Division of Hematology-Oncology, Weill Medical College of
Cornell University, New York, NY; Division of Molecular, Cell Biology
and Immunology, ImClone Systems, New York, NY; Department of
Cardiothoracic Surgery, Columbia-Presbyterian Medical Center, New York,
NY; and Division of Developmental Hematopoiesis, Sloan Kettering Cancer
Center, New York, NY.
Emerging data suggest that a subset of circulating human
CD34+ cells have phenotypic features of endothelial
cells. Whether these cells are sloughed mature endothelial cells or
functional circulating endothelial precursors (CEPs) is not known.
Using monoclonal antibodies (MoAbs) to the extracellular domain of the human vascular endothelial receptor-2 (VEGFR-2), we have shown that
1.2 ± 0.3% of CD34+ cells isolated from fetal liver
(FL), 2 ± 0.5% from mobilized peripheral blood, and 1.4 ± 0.5%
from cord blood were VEGFR-2+. In addition, most
CD34+VEGFR-2+ cells express hematopoietic
stem cell marker AC133. Because mature endothelial cells do not express
AC133, coexpression of VEGFR-2 and AC133 on CD34+ cells
phenotypically identifies a unique population of CEPs. CD34+VEGFR-2+ cells express
endothelial-specific markers, including VE-cadherin and E-selectin.
Also, virtually all CD34+VEGFR-2+ cells
express the chemokine receptor CXCR4 and migrate in response to stromal-derived factor (SDF)-1 or VEGF. To quantitate the plating efficiency of CD34+ cells that give rise to endothelial
colonies, CD34+ cells derived from FL were incubated with
VEGF and fibroblast growth factor (FGF)-2. Subsequent isolation and
plating of nonadherent FL-derived VEGFR-2+ cells with
VEGF and FGF-2 resulted in differentiation of AC133+
VEGFR-2+ cells into adherent
AC133 VEGFR-2+Ac-LDL+
(acetylated low-density lipoprotein) colonies (plating
efficiency of 3%). In an in vivo human model, we have found that the
neo-intima formed on the surface of left ventricular assist devices
is colonized with AC133+VEGFR-2+ cells.
These data suggest that circulating CD34+ cells
expressing VEGFR-2 and AC133 constitute a phenotypically and
functionally distinct population of circulating endothelial cells that
may play a role in neo-angiogenesis.

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75(3):
618 - 628.
[Abstract]
[Full Text]
[PDF]
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A. Schmidt, K. Brixius, and W. Bloch
Endothelial Precursor Cell Migration During Vasculogenesis
Circ. Res.,
July 20, 2007;
101(2):
125 - 136.
[Abstract]
[Full Text]
[PDF]
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F. Timmermans, F. Van Hauwermeiren, M. De Smedt, R. Raedt, F. Plasschaert, M. L. De Buyzere, T. C. Gillebert, J. Plum, and B. Vandekerckhove
Endothelial Outgrowth Cells Are Not Derived From CD133+ Cells or CD45+ Hematopoietic Precursors
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2007;
27(7):
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[Abstract]
[Full Text]
[PDF]
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D. Yu, X. Sun, Y. Qiu, J. Zhou, Y. Wu, L. Zhuang, J. Chen, and Y. Ding
Identification and Clinical Significance of Mobilized Endothelial Progenitor Cells in Tumor Vasculogenesis of Hepatocellular Carcinoma
Clin. Cancer Res.,
July 1, 2007;
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[Abstract]
[Full Text]
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E. Rohde, C. Bartmann, K. Schallmoser, A. Reinisch, G. Lanzer, W. Linkesch, C. Guelly, and D. Strunk
Immune Cells Mimic the Morphology of Endothelial Progenitor Colonies In Vitro
Stem Cells,
July 1, 2007;
25(7):
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[Abstract]
[Full Text]
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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.
[Abstract]
[Full Text]
[PDF]
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C. K. Kissel, R. Lehmann, B. Assmus, A. Aicher, J. Honold, U. Fischer-Rasokat, C. Heeschen, I. Spyridopoulos, S. Dimmeler, and A. M. Zeiher
Selective Functional Exhaustion of Hematopoietic Progenitor Cells in the Bone Marrow of Patients With Postinfarction Heart Failure
J. Am. Coll. Cardiol.,
June 19, 2007;
49(24):
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[Abstract]
[Full Text]
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C. V. Pfenninger, T. Roschupkina, F. Hertwig, D. Kottwitz, E. Englund, J. Bengzon, S. E. Jacobsen, and U. A. Nuber
CD133 Is Not Present on Neurogenic Astrocytes in the Adult Subventricular Zone, but on Embryonic Neural Stem Cells, Ependymal Cells, and Glioblastoma Cells
Cancer Res.,
June 15, 2007;
67(12):
5727 - 5736.
[Abstract]
[Full Text]
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D. J. Nolan, A. Ciarrocchi, A. S. Mellick, J. S. Jaggi, K. Bambino, S. Gupta, E. Heikamp, M. R. McDevitt, D. A. Scheinberg, R. Benezra, et al.
Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization
Genes & Dev.,
June 15, 2007;
21(12):
1546 - 1558.
[Abstract]
[Full Text]
[PDF]
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L. Bezuidenhout, M. Bracher, G. Davison, P. Zilla, and N. Davies
Ang-2 and PDGF-BB cooperatively stimulate human peripheral blood monocyte fibrinolysis
J. Leukoc. Biol.,
June 1, 2007;
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[Abstract]
[Full Text]
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G. Invernici, C. Emanueli, P. Madeddu, S. Cristini, S. Gadau, A. Benetti, E. Ciusani, G. Stassi, M. Siragusa, R. Nicosia, et al.
Human Fetal Aorta Contains Vascular Progenitor Cells Capable of Inducing Vasculogenesis, Angiogenesis, and Myogenesis in Vitro and in a Murine Model of Peripheral Ischemia
Am. J. Pathol.,
June 1, 2007;
170(6):
1879 - 1892.
[Abstract]
[Full Text]
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J. M. Melero-Martin, Z. A. Khan, A. Picard, X. Wu, S. Paruchuri, and J. Bischoff
In vivo vasculogenic potential of human blood-derived endothelial progenitor cells
Blood,
June 1, 2007;
109(11):
4761 - 4768.
[Abstract]
[Full Text]
[PDF]
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P. Dentelli, A. Rosso, A. Balsamo, S. Colmenares Benedetto, A. Zeoli, M. Pegoraro, G. Camussi, L. Pegoraro, and M. F. Brizzi
C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium
Blood,
May 15, 2007;
109(10):
4264 - 4271.
[Abstract]
[Full Text]
[PDF]
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A. V. R. Santhanam, L. A. Smith, T. He, K. A. Nath, and Z. S. Katusic
Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2
Circ. Res.,
May 11, 2007;
100(9):
1379 - 1388.
[Abstract]
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[PDF]
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H. D. Theiss, R. David, M. G. Engelmann, A. Barth, K. Schotten, M. Naebauer, B. Reichart, G. Steinbeck, and W.-M. Franz
Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM)
Eur. Heart J.,
May 2, 2007;
28(10):
1258 - 1264.
[Abstract]
[Full Text]
[PDF]
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S. Schwartzenberg, V. Deutsch, S. Maysel-Auslender, S. Kissil, G. Keren, and J. George
Circulating Apoptotic Progenitor Cells: A Novel Biomarker in Patients With Acute Coronary Syndromes
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2007;
27(5):
e27 - e31.
[Abstract]
[Full Text]
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A. Norden-Zfoni, J. Desai, J. Manola, P. Beaudry, J. Force, R. Maki, J. Folkman, C. Bello, C. Baum, S. E. DePrimo, et al.
Blood-Based Biomarkers of SU11248 Activity and Clinical Outcome in Patients with Metastatic Imatinib-Resistant Gastrointestinal Stromal Tumor
Clin. Cancer Res.,
May 1, 2007;
13(9):
2643 - 2650.
[Abstract]
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[PDF]
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V. Balasubramaniam, C. F. Mervis, A. M. Maxey, N. E. Markham, and S. H. Abman
Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells in the developing lung: implications for the pathogenesis of bronchopulmonary dysplasia
Am J Physiol Lung Cell Mol Physiol,
May 1, 2007;
292(5):
L1073 - L1084.
[Abstract]
[Full Text]
[PDF]
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Y. Yamada, S.-i. Yokoyama, X.-D. Wang, N. Fukuda, and N. Takakura
Cardiac Stem Cells in Brown Adipose Tissue Express CD133 and Induce Bone Marrow Nonhematopoietic Cells to Differentiate into Cardiomyocytes
Stem Cells,
May 1, 2007;
25(5):
1326 - 1333.
[Abstract]
[Full Text]
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V. L.T. Ballard and J. M. Edelberg
Stem Cells and the Regeneration of the Aging Cardiovascular System
Circ. Res.,
April 27, 2007;
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[Abstract]
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S. Caballero, N. Sengupta, A. Afzal, K.-H. Chang, S. Li Calzi, D. L. Guberski, T. S. Kern, and M. B. Grant
Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells
Diabetes,
April 1, 2007;
56(4):
960 - 967.
[Abstract]
[Full Text]
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C. Igreja, M. Courinha, A. S. Cachaco, T. Pereira, J. Cabecadas, M. G. da Silva, and S. Dias
Characterization and clinical relevance of circulating and biopsy-derived endothelial progenitor cells in lymphoma patients
Haematologica,
April 1, 2007;
92(4):
469 - 477.
[Abstract]
[Full Text]
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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):
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[Abstract]
[Full Text]
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A. Casamassimi, M. L. Balestrieri, C. Fiorito, C. Schiano, C. Maione, R. Rossiello, V. Grimaldi, V. Del Giudice, C. Balestrieri, B. Farzati, et al.
Comparison Between Total Endothelial Progenitor Cell Isolation Versus Enriched Cd133+ Culture
J. Biochem.,
April 1, 2007;
141(4):
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[Abstract]
[Full Text]
[PDF]
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P. Madeddu and C. Emanueli
Switching on Reparative Angiogenesis: Essential Role of the Vascular Erythropoietin Receptor
Circ. Res.,
March 16, 2007;
100(5):
599 - 601.
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M. Hristov, A. Zernecke, K. Bidzhekov, E. A. Liehn, E. Shagdarsuren, A. Ludwig, and C. Weber
Importance of CXC Chemokine Receptor 2 in the Homing of Human Peripheral Blood Endothelial Progenitor Cells to Sites of Arterial Injury
Circ. Res.,
March 2, 2007;
100(4):
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[Abstract]
[Full Text]
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G. L. Hoetzer, G. P. Van Guilder, H. M. Irmiger, R. S. Keith, B. L. Stauffer, and C. A. DeSouza
Aging, exercise, and endothelial progenitor cell clonogenic and migratory capacity in men
J Appl Physiol,
March 1, 2007;
102(3):
847 - 852.
[Abstract]
[Full Text]
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M. C. Yoder, L. E. Mead, D. Prater, T. R. Krier, K. N. Mroueh, F. Li, R. Krasich, C. J. Temm, J. T. Prchal, and D. A. Ingram
Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals
Blood,
March 1, 2007;
109(5):
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[Abstract]
[Full Text]
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T. Chen, H. Bai, Y. Shao, M. Arzigian, V. Janzen, E. Attar, Y. Xie, D. T. Scadden, and Z. Z. Wang
Stromal Cell-Derived Factor-1/CXCR4 Signaling Modifies the Capillary-Like Organization of Human Embryonic Stem Cell-Derived Endothelium In Vitro
Stem Cells,
February 1, 2007;
25(2):
392 - 401.
[Abstract]
[Full Text]
[PDF]
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A. O Robb, N. L Mills, D. E Newby, and F. C Denison
Endothelial progenitor cells in pregnancy
Reproduction,
January 1, 2007;
133(1):
1 - 9.
[Abstract]
[Full Text]
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G. C. Schatteman, M. Dunnwald, and C. Jiao
Biology of bone marrow-derived endothelial cell precursors
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
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[Abstract]
[Full Text]
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N. Bonaros, R. Rauf, D. Wolf, E. Margreiter, A. Tzankov, B. Schlechta, A. Kocher, H. Ott, T. Schachner, S. Hering, et al.
Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure
J. Thorac. Cardiovasc. Surg.,
December 1, 2006;
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[Abstract]
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