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.
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Abbreviations
- BMS:
-
Bare metal stent
- EC:
-
Endothelial cells
- EPC:
-
Endothelial progenitor cells
- ISR:
-
Instent restenosis
- (L)ST:
-
(Late) Stent thrombosis
- MNC:
-
Mononuclear cells
- SEM:
-
Scanning electron microscopy
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Acknowledgments
The authors would like to thank Andrea and Ute Lohmer for their excellent support in this study. The Prokinetic Energy stent was provided by Biotronik GmbH (Berlin, Germany). The sponsor had no influence on either the conducting or the evaluation of this study.
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Sedaghat, A., Sinning, JM., Paul, K. et al. First in vitro and in vivo results of an anti-human CD133-antibody coated coronary stent in the porcine model. Clin Res Cardiol 102, 413–425 (2013). https://doi.org/10.1007/s00392-013-0547-4
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DOI: https://doi.org/10.1007/s00392-013-0547-4