Adherent Platelets Recruit and Induce Differentiation of Murine Embryonic Endothelial Progenitor Cells to Mature Endothelial Cells In Vitro

Abstract

Abstract-The homing and differentiation mechanisms of endothelial progenitor cells (EPCs) at sites of vascular lesions are unclear. To investigate whether platelets play a role in the recruitment and differentiation of EPCs, we made use of a robust mouse embryonic EPC (eEPC) line that reliably differentiates to a mature endothelial phenotype. We found that platelets stimulate chemotaxis and migration of these murine eEPCs. Further, the substantial adhesion of murine eEPCs on immobilized platelets that occurs under dynamic flow conditions is inhibited by neutralizing anti-P-selectin glycoprotein ligand-1 and anti-VLA-4 (␤ 1 -integrin) monoclonal antibodies but not by anti-CD11b (a M -integrin; macrophage antigen-1). Coincubation of murine eEPCs with platelets for 5 days induced differentiation of EPCs to mature endothelial cells as verified by positive von Willebrand factor immunofluorescence and detection of Weibel Palade bodies through electron microscopy. We conclude that platelets may play a critical part in the capture and subsequent differentiation of murine eEPCs at sites of vascular lesions, revealing a possible new role of platelets in neoendothelization after vascular injury. (Circ Res. 2006;98:e2-e10.)

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…In our experiments, local tumor progression was not affected by thrombocytopenia at least when platelets were depleted in the early phase after subcutaneous tumor cell implantation. Surprisingly, although platelets have been reported to provide chemotactic signals to various cell types, including leukocytes or stem cells (4,28,36,51), we observed no effect of platelets on B16 melanoma transmigration. In contrast, we observed a robust increase in adhesivity of murine and human melanoma cells in the presence of platelets in various settings in vitro.…”

“…Static Adhesion Assay-Static adhesion assays and dynamic adhesion assays were performed as described previously (25,35,36). For static adhesion, 96-well polystyrene plates (Falcon) were coated with murine or human platelets (1 ϫ 10 8 /ml) for 2 h, washed with Tyrode's buffer to remove nonadherent platelets, and blocked for 30 min with 1% BSA in Tyrode's buffer.…”

Platelet-vessel wall interactions in atherosclerotic disease

“…Indeed,the first proof of this principle was delivered recently as isolatedplatelets were able to mediate adhesion of humanC D34 + stem cells or mousee mbryonal EPCs under arterial shearconditions (54,55). Speaking of the mouse cells this adhesion wasdependentonthe P-selectin/PSGL-1axis and β 1 -integrin (54,55).…”

“…Therefore it seems likely that platelets are capable of modifying progenitor cell biology. Indeed, when exposed to isolatedp latelets murine embryonalEPCsorhumanCD34 + stem cellscan differentiate towards mature endothelial cells ( 54,60). Furthermore, platelets seem to enhancethe biologicalpower of EPCs by increasingtheir chemotaxis andmigratorypotential (54).…”

Thérapies cellulaires pro-angiogéniques dans le traitement des pathologies ischémiques

“…Le VEGF est un candidat potentiel dont le taux augmente en conditions hypoxiques et qui induit SDF-1 dans les structures vasculaires et périvasculai-res [14]. Les chimiokines et les plaquettes permettent aussi la capture des CPE au niveau des zones de lésions vasculaires [15,16]. Une fois qu'elles ont été recrutées, les CPE se fixent sur l'endothélium activé par l'ischémie, grâce à l'action des molécules d'adhésion présentes sur la surface vasculaire comme l'intégrine 2 et la sélectine de type L [17][18][19].…”