First in vitro and in vivo results of an anti-human CD133-antibody coated coronary stent in the porcine model

Clin Res Cardiol. 2013 Jun;102(6):413-25. doi: 10.1007/s00392-013-0547-4. Epub 2013 Feb 10.

Abstract

Background: Drug-eluting stents successfully reduce restenosis at the cost of delayed re-endothelialization. A novel concept to enhance re-endothelialization is the use of antibody-coated stents which capture circulating progenitor cells. A CD34-positive-cell-capturing stent was recently developed with conflicting clinical results. CD133 is a glycoprotein expressed on circulating hematopoietic and putative endothelial-regenerating cells and may be superior to CD34.

Objective: The aim of our study was to develop a CD133-cell-capturing bare-metal stent and investigate feasibility, safety, and efficacy of CD133-stents in terms of re-endothelialization and neointima inhibition.

Methods and results: Anti-human CD133-antibodies were covalently attached to bare-metal stents. In vitro, binding capacity of CD133-stents was studied, revealing a significantly higher affinity of human CD133-positive cells to CD133-stents compared with mononuclear cells (MNCs). In vivo, 15 landrace pigs received BMS and CD133-stents in either RCX or LAD (n = 30 stents). Re-endothelialization was examined on day 1 (n = 4), 3 (n = 4) and day 7 (n = 4) using scanning electron microscopy. In histology, injury and inflammatory scores, as well as diameter restenosis were evaluated after day 7 (n = 3), 14 (n = 4), and 28 (n = 2). Overall no reduction in re-endothelialization, diameter stenosis or inflammatory score was seen with CD133-stents.

Conclusion: Stent coating with anti-human CD133-antibodies was successfully achieved with effective binding of CD133-positive cells. However, in vivo, no difference in re-endothelialization or neointima formation was evident with the use of CD133-stents compared with BMS. The low number of circulating CD133-positive cells and an increase in unspecific binding of MNCs over time may account for the observed lack of efficacy.

MeSH terms

  • AC133 Antigen
  • Animals
  • Antibodies / immunology*
  • Antigens, CD / immunology*
  • Coronary Restenosis / prevention & control
  • Coronary Stenosis
  • Endothelial Cells / metabolism
  • Feasibility Studies
  • Glycoproteins / immunology*
  • Humans
  • Inflammation / pathology
  • Leukocytes, Mononuclear / metabolism
  • Microscopy, Electron, Scanning
  • Neointima / prevention & control
  • Peptides / immunology*
  • Stents*
  • Swine
  • Time Factors

Substances

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