Anti-CD133 antibody immobilized on the surface of stents enhances endothelialization.

Jian Li,Feirong Gong,Dan Li,Hua Yu,Yi An,Shaoyan Jiang

doi:10.1155/2014/902782

Abstract

Drug eluting stents successfully reduce restenosis at the cost of delayed reendothelialization. In recent years, a novel concept to enhance reendothelialization using anti-CD34 antibody coated stents which capture circulating progenitor cells (EPCs) has been developed with conflicting clinical results. CD133 is a glycoprotein expressed on circulating hematopoietic and putative endothelial-regenerating cells and may be superior to CD34 for EPCs capture stents. In the present study, anti-CD133 antibody has been successfully immobilized to the biodegradable polymeric coating material by covalent conjugation. We explore whether anti-CD133 antibody coated stents (CD133 stents) might accelerate reendothelialization in comparison with bare metal stents (BMS) through the superior ability to capture EPCs. The in vitro cell culture results indicate that anti-CD133 antibody functionalized polymer film significantly promotes CD133 positive cells attachment and growth compared with the unfunctionalized polymer film. In the semi-in vivo arteriovenous shunt model CD133 stents demonstrate much quicker specific capturing of EPCs from the blood stream than BMS within 6 hours. In a porcine coronary artery injury model CD133 stents show more effective reendothelialization in short term compared with BMS, while no significant difference in endothelial function recovery was observed between these two groups within 6-month followup.

Highlights

Implantation of drug eluting stents (DESs) has been attracting tremendous attention as positive trial results indicate their efficacy for preventing restenosis [1,2,3]
We have proved that biomacromolecules such as heparin can be covalently immobilized to the surface of this polymer coating
After surface equilibrated with MES buffer, the polymer coated stents were activated with EDC and NHS and CD133 antibody (Milteny Biotec) was covalently immobilized on the surface of the stents which was similar to the process of CD133-PE antibody immobilization on the polymeric film surfaces

Summary

Introduction

Implantation of drug eluting stents (DESs) has been attracting tremendous attention as positive trial results indicate their efficacy for preventing restenosis [1,2,3]. The first-generation sirolimus and paclitaxel eluting stents are both associated with incomplete neointimal coverage [5, 6], impaired endothelial cell function [7], and improved risk of thrombosis formation [8]. Reendothelialization after vascular injury results either from local recruitment of adjacent endothelial cells [10] or from adhesion of blood-derived endothelial progenitor cells (EPCs) that differentiated and populate the surface of the stent [11]. A novel concept to enhance reendothelialization using antibody coated stents which capture circulating progenitor cells has been raised. We explore to fabricate surface coating with endothelial cell selectivity and rapid in situ reendothelialization by immobilizing the anti-CD133 antibody over the stent surface. We hypothesized that the immobilization of anti-CD133 antibody enhances endothelialization and may potentially be an effective therapeutic alternative to reduce safety problems for drug eluting stents

Materials and Methods

C CH2 O n

Results and Discussion