Mobilization of endothelial progenitor cells after implantation of CD34 antibody-covered sirolimus-eluting COMBO® stent: assessment with EPC colony-forming assay.

Abstract

The COMBO^® stent is a unique stent on which the CD34 antibody is mounted to capture CD34 + endothelial progenitor cells (EPCs) and from which sirolimus is eluted to suppress neointimal hyperplasia. The COMBO^® stent aims to induce early re-endothelialization and vascular healing and to prevent restenosis. In the clinical setting, however, the effects of the COMBO^® stent have not been validated in terms of EPC biology. In this study, we assessed the kinetics of circulating EPCs, not only quantitatively by flow cytometric analysis but also qualitatively by an EPC colony-forming assay, in 25 patients undergoing COMBO^® stent implantation. Among all patients, flow cytometric analysis indicated that the number of circulating CD34 + /KDR + EPCs did not change after COMBO^® stent implantation compared with baseline (before stent implantation). The EPC colony-forming assay demonstrated that the number of small-type EPC colonies increased on day 2 (3 [2, 9] to 6 [4, 9]/dish, P = 0.026) and that of large-type EPC colonies more prominently increased on day 2 (1 [0, 4] to 5 [1, 10]/dish, P < 0.001) and day 7 (to 2 [1, 7], P = 0.006) after COMBO^® stent implantation. Based on the results of optical coherence tomography at 3 months after stent implantation, the patients were divided into two groups: well (uncovered strut ratio < 10%, n = 14) and poor (uncovered strut ratio ≥ 10%, n = 10) stent coverage. Compared with baseline values, the number of large-type EPC colonies increased on day 2 (2.9 ± 0.8 to 7.3 ± 2.0, P = 0.026) and tended to increase on day 7 (6.8 ± 2.0/dish, P = 0.062) after COMBO^® stent implantation in the well coverage group, while it did not change in the poor coverage group. Thus, the COMBO^® stent might induce mature EPCs in the circulation, which might be associated with subsequent healing processes in vessel sites with stent-induced injury.