Late Outgrowth Endothelial Cells Resemble Mature Endothelial Cells and Are Not Derived from Bone Marrow§

Authors

  • Olga Tura,

    Corresponding author
    1. MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
    • Centre for Regenerative Medicine, University of Edinburgh, Scottish Centre for Regenerative Medicine, Edinburgh BioQuarter, 5 Little France Drive, Edinburgh EH16 4UU, United Kingdom
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    • Telephone: +44 131 651 9542

  • Elizabeth M. Skinner,

    1. BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • G. Robin Barclay,

    1. SNBTS Cell Therapy Research Group, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Kay Samuel,

    1. SNBTS Cell Therapy Research Group, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Ronald C.J. Gallagher,

    1. SNBTS Cell Therapy Research Group, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Mairi Brittan,

    1. MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
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  • Patrick W.F. Hadoke,

    1. BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • David E. Newby,

    1. BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Marc L. Turner,

    1. SNBTS Cell Therapy Research Group, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Nicholas L. Mills

    1. BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United KingdomUniversity of Edinburgh, Edinburgh, United Kingdom
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  • Author contributions: O.T.: conception and design, collection of data, data analysis and interpretation, and manuscript writing and final approval; E.M.S. and M.B.: collection of data and data analysis; K.S. and R.C.J.G.: collection of data, data analysis and interpretation, and manuscript writing and final approval; G.R.B., P.W.F.H., D.E.N., M.L.T., N.L.M.: conception and design, data analysis and interpretation, and manuscript writing and final approval.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 16, 2012.

Abstract

A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order to harness their potential for cardiovascular regeneration. Endothelial outgrowth cells (EOC) most closely fulfil the criteria for an EPC, but their origin remains obscure. Our aim was to identify the source and precursor of EOC and to assess their regenerative potential compared to mature endothelial cells. EOC are readily isolated from umbilical cord blood (6/6 donors) and peripheral blood mononuclear cells (4/6 donors) but not from bone marrow (0/6) or peripheral blood following mobilization with granulocyte-colony stimulating factor (0/6 donors). Enrichment and depletion of blood mononuclear cells demonstrated that EOC are confined to the CD34+CD133CD146+ cell fraction. EOC derived from blood mononuclear cells are indistinguishable from mature human umbilical vein endothelial cells (HUVEC) by morphology, surface antigen expression, immunohistochemistry, real-time polymerase chain reaction, proliferation, and functional assessments. In a subcutaneous sponge model of angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation giving rise to a similar number of vessels (7.0 ± 2.7 vs. 6.6 ± 3.7 vessels, respectively, n = 9). Bone marrow-derived outgrowth cells isolated under the same conditions expressed mesenchymal markers rather than endothelial cell markers and did not contribute to blood vessels in vivo. In this article, we confirm that EOC arise from CD34+CD133CD146+ mononuclear cells and are similar, if not identical, to mature endothelial cells. Our findings suggest that EOC do not arise from bone marrow and challenge the concept of a bone marrow-derived circulating precursor for endothelial cells. STEM CELLS2013;31:338–348

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