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Egfl7 Represses the Vasculogenic Potential of Human Endothelial Progenitor Cells

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Abstract

Egfl7 (VE-statin) is a secreted protein mostly specific to the endothelial lineage during development and in the adult and which expression is enhanced during angiogenesis. Egfl7 involvement in human postnatal vasculogenesis remains unresolved yet. Our aim was to assess Egfl7 expression in several angiogenic cell types originating from human bone marrow, peripheral blood, or cord blood. We found that only endothelial colony forming cells (ECFC), which are currently considered as the genuine endothelial precursor cells, expressed large amounts of Egfl7. In order to assess its potential roles in ECFC, Egfl7 was repressed in ECFC by RNA interference and ECFC angiogenic capacities were tested in vitro and in vivo. Cell proliferation, differentiation, and migration were significantly improved when Egfl7 was repressed in ECFC in vitro, whereas miR-126-3p levels remained unchanged. In vivo, repression of Egfl7 in ECFC significantly improved post-ischemic revascularization in a model of mouse hind-limb ischemia. In conclusion, ECFC are the sole postnatal angiogenic cells which express large amounts of Egfl7 and whose angiogenic properties are repressed by this factor. Thus, Egfl7 inhibition may be considered as a therapeutic option to improve ECFC-mediated postnatal vasculogenesis and to optimize in vitro ECFC expansion in order to develop an optimized cell therapy approach.

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Acknowledgements

We thank the animal Platform, CRP2 - UMS 3612 CNRS - US25 Inserm-IRD – Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France. We are indebted to the nursing services of Hôpital des Diaconesses (Paris) and Begin (Saint Mandé) for providing umbilical cord blood samples. This work was supported by grants from Région Ile de France-CORDDIM (Domaine d’intérêt majeur Cardiovasculaire Obésité Rein Diabète) and the Conny-Maeva Charitable Foundation. Elisa Rossi’s salary is supported by a grant from the Conny-Maeva Charitable Foundation.

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Authors and Affiliations

  1. Laboratoire de Biologie Médicale et de Greffe, Laboratoire d’Hémostase, Etablissement Français du Sang Bourgogne Franche Comté, Besançon, France

    Clément d’Audigier

  2. CHRU de Lille and INSERM UMR-S 1011, Université de Lille 2, Faculté de Médecine, EGID, Institut Pasteur de Lille, Lille, France

    Sophie Susen

  3. Sorbonne Paris Cité, Université Paris Descartes, Paris, France

    Adeline Blandinieres, Bruno Saubamea, Elisa Rossi, Nathalie Nevo, Séverine Lecourt, Blandine Dizier, Nicolas Gendron, Pascale Gaussem & David M. Smadja

  4. INSERM UMR-S 1140, Faculté de Pharmacie de Paris, Paris, France

    Adeline Blandinieres, Elisa Rossi, Nathalie Nevo, Séverine Lecourt, Blandine Dizier, Nicolas Gendron, Pascale Gaussem & David M. Smadja

  5. AP-HP, Hôpital Européen Georges Pompidou, Hematology Department, INSERM UMR-S 1140, 20 rue Leblanc, 75015, Paris, France

    Adeline Blandinieres, Nicolas Gendron, Pascale Gaussem & David M. Smadja

  6. CNRS UMR 8161, Institut Pasteur de Lille, Université de Lille, Lille, France

    Virginie Mattot, Bertrand Caetano & Fabrice Soncin

  7. Cellular and Molecular Imaging Facility, INSERM US25/CNRS UMS 3612/Faculté de Pharmacie de Paris, Paris, France

    Bruno Saubamea

  8. National Cytometry Platform, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg

    Coralie L. Guerin

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  1. Clément d’Audigier
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  2. Sophie Susen
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Correspondence to David M. Smadja.

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d’Audigier, C., Susen, S., Blandinieres, A. et al. Egfl7 Represses the Vasculogenic Potential of Human Endothelial Progenitor Cells. Stem Cell Rev and Rep 14, 82–91 (2018). https://doi.org/10.1007/s12015-017-9775-8

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