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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2634-2642. Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-06-030411. This Article Full Text Full Text (PDF) Supplemental Methods and Tables Supplemental Figures All Versions of this Article: blood-2006-06-030411v1 109/6/2634    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 Aranguren, X. L. Articles by Prósper, F. Search for Related Content PubMed PubMed Citation Articles by Aranguren, X. L. Articles by Prósper, F. Related Collections Hematopoiesis and Stem Cells Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells Xabier L. Aranguren1, Aernout Luttun2,3, Carlos Clavel1, Cristina Moreno1,4, Gloria Abizanda1, Miguel A. Barajas1,2, Beatriz Pelacho2, Maialen Uriz1, Miriam Araña1, Ana Echavarri1, Mario Soriano5, Enrique J. Andreu1, Juana Merino4, Jose Manuel Garcia-Verdugo5, Catherine M. Verfaillie2, and Felipe Prósper1 1 Hematology Service and Cell Therapy, Clínica Universitaria, Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Pamplona, Spain; 2 Stem Cell Institute, University of Minnesota Medical School, Minneapolis; 3 Center for Molecular and Vascular Biology, Catholic University of Leuven, Belgium; 4 Immunology Service, Clínica Universitaria, University of Navarra, Pamplona, Spain; 5 Department of Cell Biology, Instituto Cavanilles, University of Valencia, Spain Many stem cell types have been shown to differentiate into endothelial cells (ECs); however, their specification to arterial or venous endothelium remains unexplored. We tested whether a specific arterial or venous EC fate could be induced in human multipotent adult progenitor cells (hMAPCs) and AC133+ cells (hAC133+). In vitro, in the presence of VEGF165, hAC133+ cells only adopted a venous and microvascular EC phenotype, while hMAPCs differentiated into both arterial and venous ECs, possibly because hMAPCs expressed significantly more sonic hedgehog (Shh) and its receptors as well as Notch 1 and 3 receptors and some of their ligands. Accordingly, blocking either of those pathways attenuated in vitro arterial EC differentiation from hMAPCs. Complementarily, stimulating these pathways by addition of Delta-like 4 (Dll-4), a Notch ligand, and Shh to VEGF165 further boosted arterial differentiation in hMAPCs both in vitro and in an in vivo Matrigel model. These results represent the first demonstration of adult stem cells with the potential to be differentiated into different types of ECs in vitro and in vivo and provide a useful human model to study arteriovenous specification. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zeoli, P. Dentelli, A. Rosso, G. Togliatto, A. Trombetta, L. Damiano, P. F. di Celle, L. Pegoraro, F. Altruda, and M. F. Brizzi Interleukin-3 promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation Blood, July 15, 2008; 112(2): 350 - 361. [Abstract] [Full Text] [PDF] F. le Noble, C. Klein, A. Tintu, A. Pries, and I. Buschmann Neural guidance molecules, tip cells, and mechanical factors in vascular development Cardiovasc Res, May 1, 2008; 78(2): 232 - 241. [Abstract] [Full Text] [PDF]

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