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on January 20, 2004

Circulation. 2004
Published online before print January 20, 2004, doi: 10.1161/01.CIR.0000114522.38265.61
A more recent version of this article appeared on February 10, 2004
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© American Heart Association, Inc.

Basic Science Reports

Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells

Physiological and Therapeutic Perspectives

Valérie Planat-Benard, PhD*; Jean-Sébastien Silvestre, PhD*; Béatrice Cousin, PhD; Mireille André, MS; Maryse Nibbelink, PhD; Radia Tamarat, PhD; Michel Clergue, BSc; Carole Manneville, MS; Corinne Saillan-Barreau, PhD; Micheline Duriez, BSc; Alain Tedgui, PhD; Bernard Levy, MD, PhD; Luc Pénicaud, PhD Louis Casteilla, PhD

From Unité Mixte de Recherche 5018 Centre National de la Recherche Scientifique, Université Paul Sabatier, Centre Hospitalier Universitaire Rangueil, Toulouse (V.P.-B, B.C., M.A., M.N., C.M., C.S.-B., L.P., L.C.), and Institut National de la Santé Et de la Recherche Médicale Unité 541, Hôpital Lariboisière, Paris (J-S.S., R.T., M.C., M.D., A.T., B.L.), France.
*These authors contributed equally to this study.

Correspondence to Louis Casteilla, PhD, UMR 5018 CNRS UPS, IFR31, CHU Rangueil, 1 avenue J. Poulhès, 31054 Toulouse, France. E-mail casteil{at}toulouse.inserm.fr

Received November 7, 2003; accepted December 1, 2003.

Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease.

Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. Interestingly, dedifferentiated mature human adipocytes have the potential to rapidly acquire the endothelial phenotype in vitro and to promote neovascularization in ischemic tissue and vessel-like structure formation in Matrigel plug, suggesting that cells of endothelial and adipocyte phenotypes may have a common precursor.

Conclusions— This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor. Such adipose lineage cells participate in vascular-like structure formation in Matrigel plug and enhance the neovascularization reaction in ischemic tissue. These results also highlight the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.


Key Words: angiogenesis • ischemia • adipose tissue • therapy, cell • progenitor cells




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