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

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.

• Authors: Alexander Sedaghat, Jan-Malte Sinning, Kathrin Paul, Gregor Kirfel, Georg Nickenig, Nikos Werner
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 102 Issue 6 Pg. 413-25 (Jun 2013) ISSN: 1861-0692 [Electronic] Germany
• PMID: 23397592 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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