Endothelial progenitor cells overexpressing platelet derived growth factor-D facilitate deep vein thrombosis resolution.

Abstract

To assess the therapeutic efficacy of PDGF-D-overexpressing endothelial progenitor cells (EPCs) in deep vein thrombosis. Inferior vena cava thrombosis was induced in female Sprague Dawley (SD) rats. Animals were injected via the distal vena cava with EPCs overexpressing PDGF-D after transfection with a lentiviral vector containing the PDGF-D gene. The effect on thrombosis in animals who received EPCs was evaluated using MSB staining, immunohistochemistry, immunofluorescence, and venography; the steady-state mRNA and protein levels of PDGF-D and its receptor (PDGF-Rβ) were determined by RT-PCR and Western blotting, respectively; and the PDGF-D-induced mobilization of circulating EPCs was estimated by flow cytology. Compared with controls, injection of EPCs overexpressing PDGF-D was associated with increased thrombosis resolution; recanalization; PDGF-D and PDGF-Rβ expression; induction of monocyte homing; and mobilization of EPCs to the venous circulation. In a rat model, transplantation of PDGF-D-overexpressing EPCs facilitated the resolution of deep vein thrombosis.