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Endothelial progenitor cells: identity defined?

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      Abstract

      In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133 + cells or CD45 + haematopoietic cells.

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      Isolation of putative progenitor endothelial cells for angiogenesis.

      Putative endothelial cell (EC) progenitors or angioblasts were isolated from human peripheral blood by magnetic bead selection on the basis of cell surface antigen expression. In vitro, these cells differentiated into ECs. In animal models of ischemia, heterologous, homologous, and autologous EC progenitors incorporated into sites of active angiogenesis. These findings suggest that EC progenitors may be useful for augmenting collateral vessel growth to ischemic tissues (therapeutic angiogenesis) and for delivering anti- or pro-angiogenic agents, respectively, to sites of pathologic or utilitarian angiogenesis.
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        Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.

        Cardiovascular risk factors contribute to atherogenesis by inducing endothelial-cell injury and dysfunction. We hypothesized that endothelial progenitor cells derived from bone marrow have a role in ongoing endothelial repair and that impaired mobilization or depletion of these cells contributes to endothelial dysfunction and cardiovascular disease progression. We measured the number of colony-forming units of endothelial progenitor cells in peripheral-blood samples from 45 men (mean [+/-SE] age, 50+/-2 years). The subjects had various degrees of cardiovascular risk but no history of cardiovascular disease. Endothelium-dependent and endothelium-independent function was assessed by high-resolution ultrasonography of the brachial artery. We observed a strong correlation between the number of circulating endothelial progenitor cells and the subjects' combined Framingham risk factor score (r=-0.47, P=0.001). Measurement of flow-mediated brachial-artery reactivity also revealed a significant relation between endothelial function and the number of progenitor cells (r=0.59, P<0.001). Indeed, the levels of circulating endothelial progenitor cells were a better predictor of vascular reactivity than was the presence or absence of conventional risk factors. In addition, endothelial progenitor cells from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk. In healthy men, levels of endothelial progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease. Copyright 2003 Massachusetts Medical Society
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          Mechanisms of angiogenesis and arteriogenesis.

          Endothelial and smooth muscle cells interact with each other to form new blood vessels. In this review, the cellular and molecular mechanisms underlying the formation of endothelium-lined channels (angiogenesis) and their maturation via recruitment of smooth muscle cells (arteriogenesis) during physiological and pathological conditions are summarized, alongside with possible therapeutic applications.
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            Author and article information

            Affiliations
            [a ]Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital Ghent, De Pintelaan, Ghent, Belgium
            [b ]Department of Cardiovascular Medicine, University of Ghent, University Hospital Ghent, De Pintelaan, Ghent, Belgium
            [c ]Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
            [d ]Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
            [e ]Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA
            Author notes
            *Correspondence to: Bart VANDEKERCKHOVE, Department of Clinical Chemistry, Microbiology and Immunology, p. a. University Hospital, 4 Blok A, De Pintelaan 185, B-9000 Ghent, Belgium. Tel.: 00 32 (0)9 332 36 14 Fax: 00 32 (0)9 332 36 59 E-mail: bart.vandekerckhove@ 123456ugent.be
            Journal
            J Cell Mol Med
            J. Cell. Mol. Med
            jcmm
            Journal of Cellular and Molecular Medicine
            Blackwell Publishing Ltd (Oxford, UK )
            1582-1838
            1582-4934
            January 2009
            03 December 2008
            : 13
            : 1
            : 87-102
            19067770 3823038 10.1111/j.1582-4934.2008.00598.x
            © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
            Categories
            Reviews

            Molecular medicine

            endothelial progenitor cells, haematopoietic cells, cd34, cd45, cd133

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