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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1068-1077. Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-03-1051. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1051v1 105/3/1068    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 Tepper, O. M. Articles by Gurtner, G. C. Search for Related Content PubMed PubMed Citation Articles by Tepper, O. M. Articles by Gurtner, G. C. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Adult vasculogenesis occurs through in situ recruitment, proliferation, and tubulization of circulating bone marrow–derived cells Oren M. Tepper, Jennifer M. Capla, Robert D. Galiano, Daniel J. Ceradini, Matthew J. Callaghan, Mark E. Kleinman, and Geoffrey C. Gurtner From The Laboratory of Microvascular Research and Vascular Tissue Engineering, New York University Medical Center, New York, NY. Ischemia is a known stimulus for vascular growth. Bone marrow (BM)–derived endothelial progenitor cells (EPCs) are believed to contribute to new blood vessel growth, but the mechanism for this contribution is unknown. To elucidate how BM cells are able to form new blood vessels, a novel murine model of soft tissue ischemia was developed in lethally irradiated mice with BM reconstituted from either tie2/lacZ or ROSA/green fluorescent protein (GFP) mice (n = 24). BM-derived EPCs were recruited to ischemic tissue within 72 hours, and the extent of recruitment was directly proportional to the degree of tissue ischemia. At 7 days, there were persistently elevated levels of vascular endothelial growth factor (VEGF) (2.5-fold) and circulating VEGF receptor-2/CD11– (flk-1+/CD11–) cells (18-fold) which correlated with increased numbers of BM-derived EPCs within ischemic tissue. The cells were initially located extravascularly as proliferative clusters. By day 14, these clusters coalesced into vascular cords, which became functional vessels by day 21. In vitro examination of human EPCs from healthy volunteers (n = 10) confirmed that EPC proliferation, adhesion, and chemotaxis were all significantly stimulated in hypoxic conditions. We conclude that BM-derived cells produce new blood vessels via localized recruitment, proliferation, and differentiation of circulating cells in a sequence of events markedly different from existing paradigms of angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: EPC: the ischemia warrior of the bone marrow Edward W. Scott Blood 2005 105: 918. [Full Text] [PDF] This article has been cited by other articles: N. Derval, L. Barandon, P. Dufourcq, L. Leroux, J.-M. D. Lamaziere, D. Daret, T. Couffinhal, and C. Duplaa Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model. Eur. J. Cardiothorac. Surg., August 1, 2008; 34(2): 248 - 254. [Abstract] [Full Text] [PDF] C Kalka and I. Baumgartner Gene and stem cell therapy in peripheral arterial occlusive disease Vascular Medicine, May 1, 2008; 13(2): 157 - 172. [Abstract] [PDF] D. J. Ceradini, D. Yao, R. H. Grogan, M. J. Callaghan, D. Edelstein, M. Brownlee, and G. C. Gurtner Decreasing Intracellular Superoxide Corrects Defective Ischemia-induced New Vessel Formation in Diabetic Mice J. Biol. Chem., April 18, 2008; 283(16): 10930 - 10938. [Abstract] [Full Text] [PDF] Miyamoto K, Nishigami K, Nagaya N, et al. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation. 2006;114: 2679-2684 Perspectives in Vascular Surgery and Endovascular Therapy, March 1, 2008; 20(1): 100 - 102. [Abstract] [PDF] U. Tigges, E. G. Hyer, J. Scharf, and W. B. 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Young VEGF and PlGF promote adult vasculogenesis by enhancing EPC recruitment and vessel formation at the site of tumor neovascularization FASEB J, July 1, 2006; 20(9): 1495 - 1497. [Abstract] [Full Text] [PDF] L. Pardanaud and A. Eichmann Identification, emergence and mobilization of circulating endothelial cells or progenitors in the embryo Development, July 1, 2006; 133(13): 2527 - 2537. [Abstract] [Full Text] [PDF] S. Rafii and D. Lyden Contribution of Hematopoietic and Vascular Progenitor Cells to the Neoangiogenic Niche Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 181 - 185. [Full Text] [PDF] M. Anghelina, P. Krishnan, L. Moldovan, and N. I. Moldovan Monocytes/Macrophages Cooperate with Progenitor Cells during Neovascularization and Tissue Repair: Conversion of Cell Columns into Fibrovascular Bundles Am. J. Pathol., February 1, 2006; 168(2): 529 - 541. [Abstract] [Full Text] [PDF] J. J. Minguell and A. Erices Mesenchymal Stem Cells and the Treatment of Cardiac Disease Experimental Biology and Medicine, January 1, 2006; 231(1): 39 - 49. [Abstract] [Full Text] [PDF] N. Landazuri and W. R. Taylor The stem cell shell game. Focus on "The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture" Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1361 - C1362. [Full Text] [PDF]

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