ABSTRACT
AIMS: The Genous™ Bio-engineered R™ stent (GS) aims to promote vascular healing by capture of circulatory endothelial progenitor cells (EPCs) to the surface of the stent struts, resulting in accelerated re-endothelialization. Here, we assessed the function of the GS in comparison to bare-metal stent (BMS), when exposed to the human and animal circulation. METHODS AND RESULTS: First, 15 patients undergoing coronary angiography received an extracorporeal femoral arteriovenous (AV) shunt containing BMS and GS. Macroscopical mural thrombi were observed in BMS, whereas GS remained visibly clean. Confocal and scanning electron microscopic (SEM) analysis of GS showed an increase in strut coverage. Quantitative polymerase chain reaction (qPCR) analysis of captured cells on the GS demonstrated increased expression of endothelial markers KDR/VEGFR2 and E-selectin, and a decrease in pro-thrombogenic markers tissue factor pathway inhibitor and plasminogen activator inhibitor-1 compared with BMS. Secondly, a similar primate AV shunt model was used to validate these findings and occlusion of BMS was observed, while GS remained patent, as demonstrated by live imaging of indium-labelled platelets. Thirdly, in an in vitro cell-capture assay, GS struts showed increased coverage by EPCs, whereas monocyte coverage remained similar to BMS. Finally, the assessment of re-endothelialization was studied in a rabbit denudation model. Twenty animals received BMS and GS in the aorta and iliac arteries for 7 days. Scanning electron microscopic analysis showed a trend towards increased strut coverage, confirmed by qPCR analysis revealing increased levels of endothelial markers (Tie2, CD34, PCD31, and P-selectin) in GS. CONCLUSION: In this proof-of-concept study, we have demonstrated that the bio-engineered EPC-capture stent, Genous™ R™ stent, is effective in EPC capture, resulting in accelerated re-endothelialization and reduced thrombogenicity.
Subject(s)
Arteriovenous Shunt, Surgical/methods , Bioengineering , Coronary Artery Disease/therapy , Endothelial Cells/physiology , Stem Cells/physiology , Stents , Aged , Angioplasty, Balloon, Coronary/methods , Animals , Antigens, CD34/metabolism , Biomarkers/metabolism , Cardiac Catheterization/methods , Coronary Restenosis/prevention & control , Cytokines/metabolism , Disease Models, Animal , Endothelium, Vascular/cytology , Female , Graft Occlusion, Vascular/prevention & control , Humans , Leukocytes, Mononuclear/physiology , Male , Microscopy, Electron , Middle Aged , Papio , Platelet Adhesiveness/physiology , RabbitsABSTRACT
AIMS: To understand wound healing after drug-eluting stents (DES) placement in humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by atherectomy from bare metal stents (BMS) and DES in comparison with de novo atherosclerosis. METHODS AND RESULTS: The tissue was retrieved from ISR in ten sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS, and nine stenotic de novo atherosclerotic lesions and processed for histology and immunocytochemistry. Patients with ISR in PES showed a significantly higher incidence of unstable angina upon presentation for re-intervention (P = 0.046). De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be more proteoglycan rich. In all groups, cell content consisted almost exclusively of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present only in DES (P = 0.004), as late as 2 years following DES placement, indicating a persistent incomplete healing response. The amount of fibrinoid, given as a percentage of total tissue in each atherectomy specimen, was greater in PES than in SES (17 vs. 5%, P = 0.026). CONCLUSION: ISR in DES shows incomplete neointimal healing as late as 2 years after implantation. Patients with ISR in PES presented with more unstable angina and showed more pronounced signs of delayed healing than SES.
