SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-03-0755. This Article Full Text (PDF) All Versions of this Article: 2002-03-0755v1 101/1/168    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Salven, P. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Salven, P. Articles by Rafii, S. Social Bookmarking                   What's this? Submitted March 11, 2002 Accepted August 6, 2002 VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells Petri Salven*, Satu Mustjoki, Riitta Alitalo, Kari Alitalo, and Shahin Rafii Division of Hematology-Oncology, Weill Medical College of Cornell University, New York, NY, USA * Corresponding author; email: pjs2004{at}med.cornell.edu. Human CD133(AC133)+CD34+ stem and progenitor cells derived from fetal liver and bone marrow, and blood incorporate a functional population of circulating endothelial precursor cells. Vascular endothelial growth factor receptor 3 (VEGFR-3) regulates cardiovascular development, and physiological and pathological lymphangiogenesis and angiogenesis. However, the origin of VEGFR-3+ endothelial cells (ECs) and the mechanisms by which these cells contribute to postnatal physiological processes are not known, and the possible existence of VEGFR-3+ lymphatic or vascular EC progenitors has not been studied. Using monoclonal antibodies to the extracellular domain of VEGFR-3, we show that 11±1% of CD34+ cells isolated from human fetal liver, 1.9±0.8% CD34+ cells from human cord blood, and 0.2±0.1% of CD34+ cells from healthy adult blood donors are VEGFR-3+. CD34+VEGFR-3+ cells from fetal liver coexpress the stem/precursor cell marker CD133(AC133). Because mature endothelial cells do not express CD133, coexpression of VEGFR-3 and CD133 on CD34+ cells identifies a unique population of stem and progenitor cells. Incubation of isolated CD34+VEGFR-3+ cells in endothelial cell growth medium resulted in a strong proliferation (40-fold in 2 weeks) of nonadherent VEGFR-3+ cells. Plating of these cells resulted in the formation of adherent VEGFR-3+Ac-LDL+ (acetylated low density lipoprotein+) EC monolayers expressing various vascular and lymphatic endothelial-specific surface markers including CD34, VE-cadherin, CD51/61, CD105, LYVE-1, and podoplanin. These data demonstrate that human CD34+CD133+ cells expressing VEGFR-3 constitute a phenotypically and functionally distinct population of endothelial stem and precursor cells that may play a role in postnatal lymphangiogenesis and/or angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Pelliccia, C. Cianfrocca, G. Rosano, G. Mercuro, G. Speciale, and V. Pasceri Role of Endothelial Progenitor Cells in Restenosis and Progression of Coronary Atherosclerosis After Percutaneous Coronary Intervention: A Prospective Study J. Am. Coll. Cardiol. Intv., January 1, 2010; 3(1): 78 - 86. [Abstract] [Full Text] [PDF] F. Farace, M. Taylor, J. Rossler, Y. Loriot, and B. Besse Quantification of Circulating Vascular Endothelial Growth Factor Receptor-3-Positive Lymphatic/Vascular Endothelial Progenitor Cells Clin. Cancer Res., November 1, 2009; 15(21): 6740 - 6740. [Full Text] [PDF] K. Bogos, F. Renyi-Vamos, J. Dobos, J. Tovari, G. Ostoros, and B. Dome Clin. Cancer Res., November 1, 2009; 15(21): 6740 - 6741. [Full Text] [PDF] G. Bertolini, L. Roz, P. Perego, M. Tortoreto, E. Fontanella, L. Gatti, G. Pratesi, A. Fabbri, F. Andriani, S. Tinelli, et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment PNAS, September 22, 2009; 106(38): 16281 - 16286. [Abstract] [Full Text] [PDF] B. Gyan, B. Q. Goka, G. O. Adjei, J. K. A. Tetteh, K. A. Kusi, A. Aikins, D. Dodoo, M. L. Lesser, C. P. Sison, S. Das, et al. Cerebral Malaria Is Associated with Low Levels of Circulating Endothelial Progenitor Cells in African Children Am J Trop Med Hyg, April 1, 2009; 80(4): 541 - 546. [Abstract] [Full Text] [PDF] K. Bogos, F. Renyi-Vamos, J. Dobos, I. Kenessey, J. Tovari, J. Timar, J. Strausz, G. Ostoros, W. Klepetko, H. J. Ankersmit, et al. High VEGFR-3-positive Circulating Lymphatic/Vascular Endothelial Progenitor Cell Level Is Associated with Poor Prognosis in Human Small Cell Lung Cancer Clin. Cancer Res., March 1, 2009; 15(5): 1741 - 1746. [Abstract] [Full Text] [PDF] M. Lohela, H. Helotera, P. Haiko, D. J. Dumont, and K. Alitalo Transgenic Induction of Vascular Endothelial Growth Factor-C Is Strongly Angiogenic in Mouse Embryos but Leads to Persistent Lymphatic Hyperplasia in Adult Tissues Am. J. Pathol., December 1, 2008; 173(6): 1891 - 1901. [Abstract] [Full Text] [PDF] A. S. Arbab, B. Janic, R. A. Knight, S. A. Anderson, E. Pawelczyk, A. M. Rad, E. J. Read, S. D. Pandit, and J. A. Frank Detection of migration of locally implanted AC133+ stem cells by cellular magnetic resonance imaging with histological findings FASEB J, September 1, 2008; 22(9): 3234 - 3246. [Abstract] [Full Text] [PDF] R. S. Kerbel, R. Benezra, D. C. Lyden, K. Hattori, B. Heissig, D. J. Nolan, V. Mittal, Y. Shaked, S. Dias, F. Bertolini, et al. Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas PNAS, August 26, 2008; 105(34): E54 - E54. [Full Text] [PDF] R. G. Bagley, C. Rouleau, T. St. Martin, P. Boutin, W. Weber, M. Ruzek, N. Honma, M. Nacht, S. Shankara, S. Kataoka, et al. Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248 Mol. Cancer Ther., August 1, 2008; 7(8): 2536 - 2546. [Abstract] [Full Text] [PDF] Y. Xiao, Y. Ye, K. Yearsley, S. Jones, and S. H. Barsky The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype Am. J. Pathol., August 1, 2008; 173(2): 561 - 574. [Abstract] [Full Text] [PDF] J. Sausville, A. A. Molinolo, X. Cheng, J. Frampton, N. Takebe, J. S. Gutkind, and R. A. Feldman RCAS/SCL-TVA Animal Model Allows Targeted Delivery of Polyoma Middle T Oncogene to Vascular Endothelial Progenitors In vivo and Results in Hemangioma Development Clin. Cancer Res., June 15, 2008; 14(12): 3948 - 3955. [Abstract] [Full Text] [PDF] K. Reddy, Z. Zhou, K. Schadler, S.-F. Jia, and E. S. Kleinerman Bone Marrow Subsets Differentiate into Endothelial Cells and Pericytes Contributing to Ewing's Tumor Vessels Mol. Cancer Res., June 1, 2008; 6(6): 929 - 936. [Abstract] [Full Text] [PDF] N. Bonaros, R. Rauf, E. Werner, B. Schlechta, E. Rohde, A. Kocher, J. Bonatti, and G. Laufer Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure Interactive CardioVascular and Thoracic Surgery, April 1, 2008; 7(2): 249 - 255. [Abstract] [Full Text] [PDF] R. S. Srinivasan, M. E. Dillard, O. V. Lagutin, F.-J. Lin, S. Tsai, M.-J. Tsai, I. M. Samokhvalov, and G. Oliver Lineage tracing demonstrates the venous origin of the mammalian lymphatic vasculature Genes & Dev., October 1, 2007; 21(19): 2422 - 2432. [Abstract] [Full Text] [PDF] G. C. Furtado, T. Marinkovic, A. P. Martin, A. Garin, B. Hoch, W. Hubner, B. K. Chen, E. Genden, M. Skobe, and S. A. Lira Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid PNAS, March 20, 2007; 104(12): 5026 - 5031. [Abstract] [Full Text] [PDF] X. L. Aranguren, A. Luttun, C. Clavel, C. Moreno, G. Abizanda, M. A. Barajas, B. Pelacho, M. Uriz, M. Arana, A. Echavarri, et al. In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells Blood, March 15, 2007; 109(6): 2634 - 2642. [Abstract] [Full Text] [PDF] 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; 132(6): 1321 - 1328. [Abstract] [Full Text] [PDF] G. P. Fadini, S. V. de Kreutzenberg, A. Coracina, I. Baesso, C. Agostini, A. Tiengo, and A. Avogaro Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk Eur. Heart J., September 2, 2006; 27(18): 2247 - 2255. [Abstract] [Full Text] [PDF] K. Ikeda, R. K. Kundu, S. Ikeda, M. Kobara, H. Matsubara, and T. Quertermous Glia Maturation Factor-{gamma} Is Preferentially Expressed in Microvascular Endothelial and Inflammatory Cells and Modulates Actin Cytoskeleton Reorganization Circ. Res., August 18, 2006; 99(4): 424 - 433. [Abstract] [Full Text] [PDF] N. Ma, Y. Ladilov, J. M. Moebius, L. Ong, C. Piechaczek, A. David, A. Kaminski, Y.-H. Choi, W. Li, D. Egger, et al. Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells Cardiovasc Res, July 1, 2006; 71(1): 158 - 169. [Abstract] [Full Text] [PDF] U. Fiedler, S. Christian, S. Koidl, D. Kerjaschki, M. S. Emmett, D. O. Bates, G. Christofori, and H. G. Augustin The Sialomucin CD34 Is a Marker of Lymphatic Endothelial Cells in Human Tumors Am. J. Pathol., March 1, 2006; 168(3): 1045 - 1053. [Abstract] [Full Text] [PDF] J. Glod, D. Kobiler, M. Noel, R. Koneru, S. Lehrer, D. Medina, D. Maric, and H. A. Fine Monocytes form a vascular barrier and participate in vessel repair after brain injury Blood, February 1, 2006; 107(3): 940 - 946. [Abstract] [Full Text] [PDF] P. Religa, R. Cao, M. Bjorndahl, Z. Zhou, Z. Zhu, and Y. Cao Presence of bone marrow-derived circulating progenitor endothelial cells in the newly formed lymphatic vessels Blood, December 15, 2005; 106(13): 4184 - 4190. [Abstract] [Full Text] [PDF] H.-G. Kopp, S. T. Avecilla, A. T. Hooper, S. V. Shmelkov, C. A. Ramos, F. Zhang, and S. Rafii Tie2 activation contributes to hemangiogenic regeneration after myelosuppression Blood, July 15, 2005; 106(2): 505 - 513. [Abstract] [Full Text] [PDF] G. P. Fadini, M. Miorin, M. Facco, S. Bonamico, I. Baesso, F. Grego, M. Menegolo, S. V. de Kreutzenberg, A. Tiengo, C. Agostini, et al. Circulating Endothelial Progenitor Cells Are Reduced in Peripheral Vascular Complications of Type 2 Diabetes Mellitus J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1449 - 1457. [Abstract] [Full Text] [PDF] H. Suzuki, T. Watabe, M. Kato, K. Miyazawa, and K. Miyazono Roles of vascular endothelial growth factor receptor 3 signaling in differentiation of mouse embryonic stem cell-derived vascular progenitor cells into endothelial cells Blood, March 15, 2005; 105(6): 2372 - 2379. [Abstract] [Full Text] [PDF] Y. Aoki and G. Tosato Lymphatic Regeneration: New Insights From VEGFR-3 Blockade J Natl Cancer Inst, January 5, 2005; 97(1): 2 - 3. [Full Text] [PDF] P. Hildbrand, V. Cirulli, R. C. Prinsen, K. A. Smith, B. E. Torbett, D. R. Salomon, and L. Crisa The role of angiopoietins in the development of endothelial cells from cord blood CD34+ progenitors Blood, October 1, 2004; 104(7): 2010 - 2019. [Abstract] [Full Text] [PDF] Y. He, I. Rajantie, M. Ilmonen, T. Makinen, M. J. Karkkainen, P. Haiko, P. Salven, and K. Alitalo Preexisting Lymphatic Endothelium but not Endothelial Progenitor Cells Are Essential for Tumor Lymphangiogenesis and Lymphatic Metastasis Cancer Res., June 1, 2004; 64(11): 3737 - 3740. [Abstract] [Full Text] [PDF] A. J Makin, A. D Blann, N. A.Y Chung, S. H Silverman, and G. Y.H Lip Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells: Relationship with von Willebrand factor and tissue factor Eur. Heart J., March 1, 2004; 25(5): 371 - 376. [Abstract] [Full Text] [PDF] R. B. Colvin Emphatically Lymphatic J. Am. Soc. Nephrol., March 1, 2004; 15(3): 827 - 829. [Full Text] [PDF] C. Herder, T. Tonn, R. Oostendorp, S. Becker, U. Keller, C. Peschel, M. Grez, and E. Seifried Sustained Expansion and Transgene Expression of Coagulation Factor VIII-Transduced Cord Blood-Derived Endothelial Progenitor Cells Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2266 - 2272. [Abstract] [Full Text] [PDF] P. E. Szmitko, P. W.M. Fedak, R. D. Weisel, D. J. Stewart, M. J.B. Kutryk, and S. Verma Endothelial Progenitor Cells: New Hope for a Broken Heart Circulation, June 24, 2003; 107(24): 3093 - 3100. [Full Text] [PDF] H. Kubo and K. Alitalo The bloody fate of endothelial stem cells Genes & Dev., February 1, 2003; 17(3): 322 - 329. [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020