Surface design for in situ capture of endothelial progenitor cells: VEGF-bound surface architecture and behaviors of cultured mononuclear cells.

Abstract

In situ capture of endothelial progenitor cells (EPCs) in the arterial bloodstream may allow the creation of a functioning endothelium on the luminal surfaces of implanted cardiovascular devices. Our strategy is to use highly biospecific interaction between the cell-surface marker and surface-bound protein. The target-cell marker defined is vascular endothelial growth factor (VEGF) receptor, which is exclusively expressed on endothelial lineage cells. The candidate surface-bound proteins are VEGF and anti-VEGF receptor (VEGF-R1 and VEGF-R2) antibodies, which were covalent-bound on poly(ethylene-co-vinyl alcohol) bearing a high-surface density of hydroxyl groups. Incubating human mononuclear cells on these substrates affected the histochemical expression of cell-surface markers specific for EPCs and endothelial cells (ECs). The VEGF-bound surface significantly increased the number of cells expressing both VEGF receptors after 1 or 2 weeks of culture, whereas both anti-VEGF receptor antibody-bound substrates did not affect the expression of the surface markers, and cells on these surfaces were eventually died. These results indicate that, among the three candidate molecules, VEGF is best able to capture EPCs and induces their differentiation. Additionally, a pilot study of surface architecture of stents and small-diameter artificial grafts was conducted for an ongoing implantation study in a porcine model.