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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:644.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Ex Vivo Priming of Endothelial Progenitor Cells With SDF-1 Before Transplantation Could Increase Their Proangiogenic Potential

Faouzia Zemani; Jean-Sébastien Silvestre; Françoise Fauvel-Lafeve; Arlette Bruel; José Vilar; Ivan Bieche; Ingrid Laurendeau; Isabelle Galy-Fauroux; Anne Marie Fischer; Catherine Boisson-Vidal

From INSERM U765 (F.Z., I.G.-F., A.M.F., C.B.-V.); INSERM U689 (J.-S.S., J.V.), Cardiovascular Research Center; INSERM U553 (F.F.-L., A.B.); Université Paris Denis Diderot (J.-S.S., F.F.-L., A.B., J.V.); INSERM U745 (I.B., I.L.), Laboratoire de Génétique Moléculaire; Université Paris Descartes (I.B., I.L., I.G.-F., A.M.F.), Faculté de Médecine; IFR 105 (F.F.-L., A.B.), Institut d’Hématologie; AP-HP (A.M.F.), Hôpital Européen Georges Pompidou, Service d’Hématologie Biologique, Paris, France.

Correspondence to Dr Catherine Boisson-Vidal, INSERM U765, Faculté de Pharmacie 4 av. de l’Observatoire, 75270 Paris, France. E-mail catherine.boisson-vidal{at}univ-paris5.fr

Objectives— As SDF-1 and its cognate receptor CXCR4 play a key role in the survival and mobilization of immature cells, we examined whether preconditioning of endothelial progenitor cells (EPCs) with SDF-1 could further promote their capacity to enhance angiogenesis.

Methods and Results— EPC exposure to 100 ng/mL SDF-1 for 30 min induced a proangiogenic phenotype, with cell migration and differentiation into vascular cords in Matrigel and increased their therapeutic potential in a nude mouse model of hindlimb ischemia. This pretreatment enhanced EPC adhesion to activated endothelium in physiological conditions of blood flow by stimulating integrin-mediated EPCs binding to endothelial cells. Pretreated EPCs showed significantly upregulated surface 4 and M integrin subunit expression involved in the homing of immature cells to a neovasculature and enhanced FGF-2 and promatrix metalloproteinase (MMP)-2 secretion. All these effects were significantly attenuated by EPC incubation with AMD-3100, a CXCR4 antagonist, by prior HSPGs disruption and by HUVEC incubation with anti–intercellular adhesion molecule1 (ICAM-1) and anti–vascular cell adhesion molecule (VCAM) blocking antibodies. Pretreated EPCs adhered very rapidly (within minutes) and were resistant to shear stresses of up to 2500s^–1.

Conclusions— SDF-1 pretreatment during EPC expansion stimulates EPC adhesion to endothelial cells and thus augments the efficiency of cell therapy for ischemic vascular diseases.

EPC exposure to SDF-1 for 30 min induced a proangiogenic phenotype, enhancing not only the ability of these cells to adhere to activated endothelium but also promoting tube formation, via integrin-, CXCR4-, and HSPGs-dependent mechanisms. Subsequently, SDF-1–treated EPCs displayed a marked therapeutic potential in a model of mice hindlimb ischemia.

Key Words: endothelial progenitor cells • SDF-1 • ischemia • HSPGs • adhesion

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Geoffrey C. Gurtner and Edwin Chang
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