Hydroxybutyl Chitosan Polymer-Mediated CD133 Antibody Coating of Metallic Stents to Reduce Restenosis in a Porcine Model of Atherosclerosis

J Cardiovasc Pharmacol Ther. 2015 May;20(3):322-9. doi: 10.1177/1074248414558518. Epub 2014 Nov 19.

Abstract

Antibody-coated stents to capture circulating endothelial progenitor cells (EPCs) for re-endothelialization appear to be a novel therapeutic option for the treatment of atherosclerotic disease. Hydroxybutyl chitosan (HBC), a linear polysaccharide made from shrimps and other crustacean shells, is biocompatible, nontoxic, and hydrophilic, making it ideal for biomedical applications. In this study, HBC was explored for the immobilization of anti-CD133 antibodies. We demonstrated that CD133 antibodies mediated by HBC were successfully coated on cobalt-chromium alloy discs and metal stents. The coating was homogeneous and smooth as shown by electronic microscopy analysis. Balloon expansion of coated stents did not cause cracking or peeling. The HBC discs promoted CD133+ EPCs and human umbilical vein endothelial cell growth in vitro. The CD133 antibody-coated but not bare discs bound CD133+ EPCs in vitro. Implantation of CD133 antibody-coated stents significantly inhibited intimal hyperplasia and reduced restenosis compared with implantation of bare stents in a porcine model of atherosclerosis. These findings suggest HBC is a valuable anchoring agent that can be applied for bioactive coating of stents and that CD133 antibody-coated stents might be a potential therapeutic alternative for the treatment of atherosclerotic disease.

Keywords: CD133 antibody; endothelial progenitor cells; hydroxybutyl chitosan; re-endothelialization; restenosis; stent coating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antibodies, Immobilized / administration & dosage*
  • Antigens, CD / immunology*
  • Atherosclerosis / therapy*
  • Cell Proliferation
  • Cells, Cultured
  • Chitosan / administration & dosage*
  • Endothelial Progenitor Cells / physiology*
  • Glycoproteins / immunology*
  • Humans
  • Hyperplasia
  • Male
  • Neointima / pathology
  • Peptides / immunology*
  • Polymers / administration & dosage*
  • Stents*
  • Swine

Substances

  • AC133 Antigen
  • Antibodies, Immobilized
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Polymers
  • Chitosan