Haase Daniela, Otto Sylvia, Romeike Bernd F M, Figulla Hans R, Poerner Tudor C
Clinic of Internal Medicine I, Jena University Hospital, Friedrich Schiller University of Jena, Germany.
Institute of Pathology, Jena University Hospital, Friedrich Schiller University of Jena, Germany.
ALTEX. 2015;32(4):307-317. doi: 10.14573/altex.1503051. Epub 2015 Sep 24.
One of the main limitations of percutaneous coronary interventions is the restenosis, occurring in small-diameter arteries, and efforts are high to find improved intracoronary devices to prevent in-stent-restenosis. 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) and drug eluting stents (DES), respectively, 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. We have found that cells formed multiple layers after three months, and the detection with both CD31 and a-smooth muscle actin 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 appear as an initial benchmark for testing new anti-proliferative endovascular therapies and consequently helps to reduce animal experiments in this research area.
经皮冠状动脉介入治疗的主要局限性之一是再狭窄，其发生于小直径动脉，因此人们致力于寻找改良的冠状动脉内装置以预防支架内再狭窄。本研究的目的是建立一个用于再狭窄研究的新的体外测试平台，适用于支架血管内的长期细胞增殖和迁移研究。获取新鲜猪冠状动脉节段进行去细胞处理，然后接种人冠状动脉内皮细胞（HCAEC）和人冠状动脉平滑肌细胞（HCASMC）。随后，分别植入裸金属支架（BMS）和药物洗脱支架（DES），并再次接种HCAEC和HCASMC，持续三个月。在第0、2、4、6、8和12周时，通过组织化学和免疫组织化学特征对支架血管节段进行检查，并测量支架植入前后的接种区域。我们发现三个月后细胞形成了多层，用CD31和α-平滑肌肌动蛋白特异性抗体检测表明，HCAEC和HCASMC粘附并多层生长。此外，我们发现与BMS（17%±2.3%）相比，DES的增殖面积显著更小（70%±3.5%）。这些数据与动物和人体研究结果相似。因此，该血管模型可能作为测试新型抗增殖血管内治疗方法的初步基准，从而有助于减少该研究领域的动物实验。
