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This Article Full Text Full Text (PDF) 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 Peichev, M. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Peichev, M. Articles by Rafii, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  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 AC133VEGFR-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. V. Busik, M. Tikhonenko, A. Bhatwadekar, M. Opreanu, N. Yakubova, S. Caballero, D. Player, T. Nakagawa, A. Afzal, J. Kielczewski, et al. 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