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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 (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 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Aranguren, X. L Articles by Prosper, F. Search for Related Content PubMed PubMed Citation Articles by Aranguren, X. L Articles by Prosper, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 21, 2006 Accepted October 29, 2006 In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells Xabier L Aranguren, Aernout Luttun, Carlos Clavel, Cristina Moreno, Gloria Abizanda, Miguel A Barajas, Beatriz Pelacho, Maialen Uriz, Miriam Arana, Ana Echavarri, Mario Soriano, Enrique J Andreu, Juana Merino, Jose Manuel Garcia-Verdugo, Catherine M Verfaillie, and Felipe Prosper* Hematology Service & Cell Therapy, University of Navarra, Pamplona, Spain Center for Molecular & Vascular Biology, Catholic University of Leuven, Belgium Division of Immunology Service, University of Navarra, Pamplona, Spain Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, United States Dept of Cell Biology, Instituto Cavanilles, University of Valencia, Spain * Corresponding author; email: fprosper{at}unav.es. 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 arterio-venous specification. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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