O4	Interaction of embryonal endothelial progenitor cells with platelets.
1H.Langer, 1A.May, 2S.Massberg, 3A.K.Hatzopoulos, 4U.Heinzmann, 1M.Gawaz
1Medizinische Klinik, Abteilung III, Universitätsklinikum, Tübingen, DE; 2Deutsches Herzzentrum, München, DE; 3Institute for Clinical Molecular Biology and Tumor Genetics, München, DE; 4GSF-Research Center for Environment & Health, Institute of Pathology, München, DE.

The homing and differentiation of endothelial progenitor cells (EPCs) is not fully understood. We investigated, if EPCs adhere to platelets and if platelets can influence the biological development of EPC. Methods and Results: The murine embryonal EPC line T17b was found to extensively express CD162 (PSGL-1) and CD49d (VLA-4) on their surface. Consistently, EPCs tethered onto collagen-bound, adherent platelets in a PSGL-1- and p-selectin-dependent manner under arterial flow conditions, whereas firm adhesion to adherent platelets was mediated by β1-integrins. In accordance, EPCs specifically adhered to the ligand of VLA-4, fibronectin, but not to the major components of the extracellular matrix, collagen I or von Willebrand Factor (vWF). Coincubation of EPCs with platelets induced differentiation of EPCs into mature endothelial cells as evidenced by typical morphological changes, acquired expression of endothelium-specific markers (vWF, PECAM-1) (flow cytometry, immunofluorescence microscopy) and of Weibel Pallade bodies (transmission electron microscopy), loss of the stem cell marker c-kit (RT-PCR), and typical functional changes: Platelets enhanced the migratory capacity of EPCs in a scratch assay and a platelet clot was covered by differentiated EPCs after 7 days indicating a beginning “endothelialization”. Conclusion: Platelets can recruit circulating EPCs to sites of exposed extracellular matrix via binding of PSGL-1 to p-selectin and β1-integrins to fibronectin in vitro, and can initiate EPC differentiation into endothelial cells.

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