Pathways Mediating the Interaction between Endothelial Progenitor Cells (EPCs) and Platelets

INTRODUCTION: Endothelial progenitor cells (EPCs) have an important role in the process of vascular injury repair. Platelets have been shown to mediate EPC recruitment, maturation and differentiation. Yet, the mechanism underlying this interaction is unclear. We, therefore, aimed to examine whether direct contact between platelets and EPCs is essential for the positive platelets-EPC effect, and to investigate the main mediators responsible for the improvement in EPCs function. METHODS: Human EPCs were isolated from donated buffy coats and cultured in either: 1. EPCs co-incubated with platelets placed in a 1 µm-Boyden chamber. 2. EPCs incubated with or without platelets in the presence or absence of bFGF/PDGF Receptor inhibitor (PDGFRI). After 7 days culture, EPCs ability to form colonies, proliferate and differentiate was examined. Culture supernatants were collected and growth factors levels were evaluated using ELISA. Growth factors mRNA levels in EPCs were evaluated using RT-PCR. RESULTS AND CONCLUSIONS: After 7 days culture, EPCs functional properties were higher following co-incubation with platelets (directly or indirectly), implying that direct contact is not essential for the platelet’s positive effect on EPCs. This effect was reduced by PDGFRI inhibition. Additionally, higher levels of PDGFB in EPCs-platelets supernatant and higher levels of PDGFC mRNA in EPCs co-incubated with platelets were found. In contrast, FGF and other potential mediators that were examined and inhibited did not significantly affect the interaction between platelets and EPCs. Thus, we conclude that PDGF has a central role in the interaction between platelets and EPCs. Further study is required to examine additional aspects of EPC-platelets interaction.