Stem Cell Reviews and Reports

, Volume 13, Issue 4, pp 552–560 | Cite as

Human very Small Embryonic-like Cells Support Vascular Maturation and Therapeutic Revascularization Induced by Endothelial Progenitor Cells

  • Coralie L. Guerin
  • Elisa Rossi
  • Bruno Saubamea
  • Audrey Cras
  • Virginie Mignon
  • Jean-sébastien Silvestre
  • David M. Smadja


Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells defined as cells of small size being Lineage- negative, CD133-positive, and CD45-negative. We previously described that human bone marrow VSELs were able to differentiate into endothelial cells and promoted post-ischemic revascularization in mice with surgically induced critical limb ischemia. In the present work, we isolated bone marrow VSELs from patients with critical limb ischemia and studied their ability to support endothelial progenitor cells therapeutic capacity and revascularization potential. Sorted bone marrow VSELs cultured in angiogenic media were co-injected with endothelial progenitor cells and have been show to trigger post-ischemic revascularization in immunodeficient mice, and support vessel formation in vivo in Matrigel implants better than human bone marrow mesenchymal stem cells. In conclusion, VSELs are a potential new source of therapeutic cells that may give rise to cells of the endothelial and perivascular lineage in humans. VSELs are the first real vasculogenic stem cells able to differentiate in endothelial and perivascular lineage in human adult described from now. Thus, because VSELs presence have been proposed in adult tissues, we think that VSELs are CD45 negative stem cells able to give rise to vascular regeneration in human tissues and vessels.


Very small embryonic like cells VSEL Endothelial progenitor cells ECFC Vasculogenesis Perivascular cells 



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’salary is supported by a grant from Conny-Maeva Charitable Foundation.

Compliance with Ethical Standards

Conflict of Interest

Authors declare no conflict of interest related to this work.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Coralie L. Guerin
    • 1
  • Elisa Rossi
    • 2
    • 3
  • Bruno Saubamea
    • 4
  • Audrey Cras
    • 2
    • 3
    • 5
  • Virginie Mignon
    • 4
  • Jean-sébastien Silvestre
    • 2
    • 6
  • David M. Smadja
    • 2
    • 3
    • 7
  1. 1.National Cytometry Platform, Department of Infection and ImmunityLuxembourg Institute of HealthStrassenLuxembourg
  2. 2.Université Paris Descartes, Sorbonne Paris CitéParisFrance
  3. 3.Inserm UMR-S1140ParisFrance
  4. 4.Cellular and Molecular Imaging Facility, Inserm US 25, CNRS UMS 3612, Faculty of Pharmacy of ParisParis Descartes UniversityParisFrance
  5. 5.Cell Therapy DepartmentAP-HP, Saint Louis HospitalParisFrance
  6. 6.Inserm UMRS-970, Paris Centre de Recherche CardiovasculaireParisFrance
  7. 7.Hematology DepartmentAP-HP, European Georges Pompidou HospitalParisFrance

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