Development and characterization of an ex vivo arterial long-term proliferation model for restenosis research

Abstract

One of the main limitations of percutaneous coronary interventions is restenosis, occurring in small-diameter arteries. Many efforts are underway to find improved intracoronary devices to prevent in-stent restenosis. The aim of this study was to produce a new in vitro test platform for restenosis research, suitable for long-term cell proliferation and migration studies in stented vessels. Fresh segments of porcine coronary arteries were obtained for decellularization and were then reseeded with human coronary artery endothelial (HCAEC) and human coronary artery smooth muscle cells (HCASMC). Subsequently, bare metal stents (BMS) or drug eluting stents (DES) were implanted and the segments were reseeded with HCAEC and HCASMC for up to three months. The stented segments were examined at time zero and after 2, 4, 6, 8 and 12 weeks by histochemical and immunohistochemical characterization and the reseeded areas before and after stent implantation were measured. Cells formed multiple layers after three months and detection of both CD31 and α-smooth muscle actin by specific antibodies showed that HCAEC and HCASMC are adherent and growing in several layers. Furthermore, we could show a significantly smaller proliferation area in DES (70% ± 3.5%) compared to BMS (17% ± 2.3%). These data are similar to animal and human studies. Therefore, this vessel model might be suitable as an initial benchmark for testing new anti-proliferative endovascular therapies and could consequently help to reduce animal experiments in this research area.