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

Abstract

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 ϩ stem cells. We evaluated the role of platelet-derived SDF-1 in adhesion and differentiation of human CD34 ϩ cells into endothelial progenitor cells. Methods and Results-Adherent platelets express substantial amounts of SDF-1 and recruit CD34 ϩ 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 ϩ 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 ϩ cells in microcirculation. Moreover, platelet-derived SDF-1 binding to CXCR4 receptor promotes platelet-induced differentiation of CD34 ϩ cells into endothelial progenitor cells, as verified by colony-forming assays in vitro. Conclusions-These

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

“…1). It is known that platelets express and secrete the CXC chemokine SDF-1␣ (CXCL12), which has recently been implicated in attracting circulating cells to the vascular wall (27,42,43). Expression of the cognate receptor for SDF-1␣, CX-chemokine receptor 4 (CXCR4) has been shown to crucially support organ-selective hematogenous metastasis of melanoma cells to the lung (32).…”

“…Human platelets were isolated as described previously (25)(26)(27). Briefly, venous blood was drawn from the antecubital vein of healthy volunteers and collected in acid/citrate/dextrose buffer.…”

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…Platelet activation through ADP-receptor (P2Y12), GPVI and protease activated receptor-1 (PAR1) ligation drives SDF-1α (CXCL12) release (23) (▶ Figure 1) and enhances migration and differentiation of endothelial progenitor cells at the sites of vascular injury to promote regeneration (24,25). Platelet-derived-SDF-1α also promotes the differentiation of CD34 + cells into macrophages and foam cells and thereby contributes to vascular inflammation (26).…”

Platelet-vessel wall interactions in atherosclerotic disease

“…Therefore alsoc ontraproductive effects arem ediatedb yp latelet-EPCi nteraction, which canb ec ontrolled in vitro by the application of statins (60,63). Amajormolecule involved in platelet-mediated effects on progenitor cellsseems to be the chemokine SDF-1, as platelet-derivedSDF-1 regulates recruitment, proliferation anddifferentiation of progenitor cells, a mechanismmostlikelycontributing to vascularrepair andregeneration of ischemicm yocardium (23,24,64). Moreover,i nhibition of the SDF-1/ CXCR4 axis preventedrecruitment of progenitor cellstovascular lesions in vivo (64,65).…”