Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells

Bruno Delorme; Agnès Basire; Carla Gentile; Florence Sabatier; Frédéric Monsonis; Christophe Desouches; Marcel Blot-Chabaud; Georges Uzan; José Sampol; Françoise Dignat-George

doi:10.1160/TH05-07-0499

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(06): 1270-1279
DOI: 10.1160/TH05-07-0499

Endothelium and Vascular Development

Schattauer GmbH

Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146⁺ blood cells

Bruno Delorme

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

,

Agnès Basire

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

,

Carla Gentile

³INSERM Unité 602, Groupe Hospitalier Paul Brousse, Villejuif, France

,

Florence Sabatier

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

²Laboratoire d’Hématologie, Centre Hospitalier Universitaire La Conception, Marseille, France

,

Frédéric Monsonis

⁴Beckman Coulter Immunotech Company, Marseille, France

,

Christophe Desouches

⁵Service de Chirurgie Plastique, Réparatrice et Esthétique, Centre Hospitalier Universitaire La Conception, Marseille, France

,

Marcel Blot-Chabaud

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

,

Georges Uzan

³INSERM Unité 602, Groupe Hospitalier Paul Brousse, Villejuif, France

,

José Sampol

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

²Laboratoire d’Hématologie, Centre Hospitalier Universitaire La Conception, Marseille, France

,

Françoise Dignat-George

¹INSERM Unité 608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France

²Laboratoire d’Hématologie, Centre Hospitalier Universitaire La Conception, Marseille, France

› Author Affiliations

Abstract

Summary

CD146 is an adhesion molecule present on endothelial cells throughout the vascular tree. CD146 is also expressed by circulating endothelial cells (CECs) widely considered to be mature endothelial cells detached from injured vessels. The discovery of circulating endothelial progenitor cells (EPCs) originating from bone marrow prompted us to investigate whether CD146 circulating cells could also contains EPCs. We tested this hypothesis using an approach combining elimination of CECs by an adhesion step, followed by immunomagnetic sorting of remaining CD146⁺ cells from the non adherent fraction of cord blood mononuclear cells. When cultured under endothelial-promoting conditions, these cells differentiated as late outgrowth endothelial colonies: they grew as a cobblestone monolayer, were uniformly positive for endothelial markers and did not express leukocyte antigens. They highly proliferated and were expanded in long-term culture without alterations of their phenotypic and functional properties (DiI-ac-LDL uptake, wound repair, capillary-like network formation, and TNFα response). Moreover, these cells colonized a Matrigel plug in immunodeficient mice (NOD/SCID). Finally, using 4-color flow cytometry analysis of purified CD34+ cells, we clearly discriminated, CD146⁺ EPCs (CD146⁺ CD34⁺ CD45⁺ CD133⁺ or CD117⁺), and CD146⁺ CECs (CD146⁺ CD34⁺, CD45⁻ CD133⁻ or CD117⁻), both in cord and adult peripheral blood. The relative proportions of the two CD146⁺ subsets varied in patients with myocardial infarction as compared to healthy subjects. Our study establishes that, beside CECs, CD146⁺ circulating cells contain a subpopulation of EPCs with potential use in proangiogenic therapy. In addition, the dual measurement of CD146⁺ CECs and CD146⁺ EPCs offers a promising tool for monitoring vascular injury/regeneration processes in clinical situations.

Keywords

CD146 - angiogenesis - myocardial infarction - circulating endothelial cells - progenitor endothelial cells

Full Text

References

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