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

Authors:
  • AMAndreas Eberhard May
    Andreas Eberhard May
  • KDKarin Daub
    Karin Daub
  • UHUlrich Heinzmann
    Ulrich Heinzmann
  • PLPeter Lang
    Peter Lang
  • MSMichael Schumm
    Michael Schumm
  • SMSteffen Massberg
    Steffen Massberg
  • TSTanja SchönBerger
    Tanja SchönBerger
  • IPIris Pfisterer
    Iris Pfisterer
  • AHAntonis K. Hatzopoulos
    Antonis K. Hatzopoulos
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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 (β 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.

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