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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-03-0755. This Article Full Text 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 January 2003, Vol. 101, No. 1, pp. 168-172 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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 From the Division of Hematology-Oncology, Weill Medical College of Cornell University, New York, NY; and Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital, Biomedicum Helsinki, University of Helsinki, Finland. Human CD133 (AC133)+CD34+ stem and progenitor cells derived from fetal liver and from 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 positive for VEGFR-3. CD34+VEGFR-3+ cells from fetal liver coexpress the stem/precursor cell marker CD133 (AC133). Because mature ECs 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 EC 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+ (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. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Sausville, A. A. Molinolo, X. Cheng, J. Frampton, N. Takebe, J. S. Gutkind, and R. A. 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