Vascular endothelial growth factor-bound stents: application of in situ capture technology of circulating endothelial progenitor cells in porcine coronary model.

Objectives: We evaluated the in vivo performance of a newly devised vascular endothelial growth factor (VEGF)-bound stent in a porcine coronary model.

Background: An anti-CD34 antibody-bound stent, which captures endothelial progenitor cells (EPCs) to accelerate tissue formation, did not reduce intimal hyperplasia. By targeting the VEGF receptor, which is expressed on endothelial-lineage cells, we developed VEGF-bound stents that may enable selective capture of EPCs followed by rapid endothelialization.

Methods: Metallic stents were first coated with poly-(ethylene-co-vinyl alcohol), and then chemically bound with either VEGF or anti-CD34 antibody. These stents were placed in porcine coronary arteries for up to 14 days. Stent surface was evaluated by immunohistochemistry and by scanning electron microscope (SEM).

Results: After 2-day stenting with VEGF-bound stents, small populations of KDR (VEGF receptor-2)-positive cells adhered to the stent struts. After 7- and 14-day stenting, struts were fully covered with newly regenerated tissue. SEM images showed that the uniform tissue formed on struts was morphologically similar to native endothelium and was continuously connected with adjacent native endothelium. On the other hand, for the anti-CD34 antibody-bound stents, stent struts were rapidly covered by newly generated tissue that consisted of multicellular aggregates.

Conclusions: Compared with anti-CD34 antibody-bound stents, VEGF-bound stents provide highly selective capture of EPCs, followed by rapid formation of intact endothelium tissue at an early period of stenting. These results suggest that VEGF-bound stents could represent a promising therapeutic option for cardiovascular stenting, although further long-term follow-up experiment with double-blinded fashion is needed prior to clinical application.