Anti-CD133 Antibody Immobilized on the Surface of Stents Enhances Endothelialization

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.

Covalent Polyisobutylene–Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings

“…[28][29][30][31] The conjugation of antibodies aimed at capturing endothelial progenitor cells to promote re-endothelialization are also being explored. 32, 33 Nevertheless, there are limitations to all of these systems and the ideal stent coating has not yet been developed.…”

Adding Functions to Biomaterial Surfaces through Protein Incorporation

“…Most prominent amongst these has been CD133, antibodies against which have been reported to mediate efficient EC/EPC coating of bare metal stents in vitro. [160] The lack of re-endothelialization or neointima formation mediated by anti-CD133 antibodies on bare metal stents in a porcine model, [161] however, highlights the difficulties in extrapolating from laboratory assays that are typically based on pure cell cultures, may not incorporate flow, and typically utilize significantly higher cell densities than obtaining in vivo. An antibody against vascular endothelial-cadherin has also been proposed to accelerate endothelial recovery and reduce neointimal formation on stainless steel stents compared with CD34-capture stents, [162] while endoglin/CD105, a type III accessory receptor for the transforming growth factor (TGF)-β superfamily, has also been identified as a potential cell marker, [163] and stainless steel stents coated with anti-endoglin immunoglobulins have been reported to perform as well as the Genous™ stent in porcine studies.…”

Antibody-Based Capture and Behaviour of Endothelial Cell Lines on Pre-Surface Modified Medical Grade Steel

“…Finally, re-endothelialization of both injured, natural vascular tissue, and implanted stents for the prevention of platelet aggregation has attracted considerable attention over the years [20][21][22][23][24][25][26][27][28][29]. With specific regard to the latter biologically-active surface coatings with the capacity to capture circulating endothelial cells have been proposed.…”