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(Circulation. 2008;117:206-215.)
© 2008 American Heart Association, Inc.

Molecular Cardiology

Platelet-Derived Stromal Cell–Derived Factor-1 Regulates Adhesion and Promotes Differentiation of Human CD34⁺ Cells to Endothelial Progenitor Cells

Konstantinos Stellos, MD; Harald Langer, MD; Karin Daub, PhD; Tanja Schoenberger, DVM; Alexandra Gauss, DVM; Tobias Geisler, MD; Boris Bigalke, MD; Iris Mueller, MD; Michael Schumm, DVM; Iris Schaefer, BSc; Peter Seizer, MD; Bjoern F. Kraemer, MD; Dorothea Siegel-Axel, PhD; Andreas E. May, MD; Stephan Lindemann, MD; Meinrad Gawaz, MD

From Medizinische Klinik III (K.S., H.L., K.D., T.S., A.G., T.G., B.B., I.M., I.S., P.S., B.F.K., D.S.-A., A.E.M., S.L., M.G.) and Kinderklinik (M.S.), Eberhard Karls-Universität Tübingen, Tübingen, Germany.

Correspondence to Meinrad Gawaz, MD, Medizinische Klinik III, Universitätsklinikum Tübingen, Otfried-Müller Straße 10, 72076 Tübingen, Germany. E-mail meinrad.gawaz{at}med.uni-tuebingen.de

Received May 10, 2007; accepted October 22, 2007.

Background— Peripheral homing of progenitor cells in areas of diseased organs is critical for tissue regeneration. The chemokine stromal cell–derived factor-1 (SDF-1) regulates homing of CD34⁺ stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34⁺ cells into endothelial progenitor cells.

Methods and Results— Adherent platelets express substantial amounts of SDF-1 and recruit CD34⁺ cells in vitro and in vivo. A monoclonal antibody to SDF-1 or to its counterreceptor, CXCR4, inhibits stem cell adhesion on adherent platelets under high arterial shear in vitro and after carotid ligation in mice, as determined by intravital fluorescence microscopy. Platelets that adhere to human arterial endothelial cells enhance the adhesion of CD34⁺ cells on endothelium under flow conditions, a process that is inhibited by anti-SDF-1. During intestinal ischemia/reperfusion in mice, anti-SDF-1 and anti-CXCR4, but not isotype control antibodies, abolish the recruitment of CD34⁺ cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation of CD34⁺ cells into endothelial progenitor cells, as verified by colony-forming assays in vitro.

Conclusions— These findings imply that platelet-derived SDF-1 regulates adhesion of stem cells in vitro and in vivo and promotes differentiation of CD34⁺ cells to endothelial progenitor cells. Because tissue regeneration depends on recruitment of progenitor cells to peripheral vasculature and their subsequent differentiation, platelet-derived SDF-1 may contribute to vascular and myocardial regeneration.

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