Accelerated vascular repair following percutaneous coronary intervention by capture of endothelial progenitor cells promotes regression of neointimal growth at long term follow-up: final results of the Healing II trial using an endothelial progenitor cell capturing stent (Genous R stent)™

Abstract

Aims: The study sought to define the long-term angiographic and clinical outcome of a bio-engineered stent, able to sequester endothelial progenitor cells (EPC) to the stent to promote the post-stenting vascular repair response. Methods and results: The HEALING-II was a multicentre, prospective registry, including 63 patients treated with the implantation of a Genous™ EPC capture stent. Serial quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) analysis was performed at 6 and 18 month. The 18 month composite MACE rate was 7.9%, whereas 6.3% clinically justified target lesion revascularisations were observed. Although patients received one month of clopidogrel, no (sub)acute or late angiographic stent thrombosis occurred. At 6 month follow-up, in-stent late luminal loss was 0.78±0.39 mm and percent in-stent volume obstruction was 22.9±13.7% (mean±sd). Serial angiographic and IVUS analyses were available in 30 event-free patients at post-procedure, 6 months and 18 months. From 6 months to 18 months follow-up, a significant late regression of neointimal hyperplasia was observed on QCA (late luminal loss 0.59±0.31, 24.4% reduction or 16.9% by matched serial analysis) and IVUS (percent instent volume obstruction 20.3±14.3%, 11.4% reduction or 9.6% by matched serial analysis). The relative increase in circulating EPC titers at long-term follow-up correlated with neointimal compaction in individual patients, suggestive of an EPC-mediated vascular repair response. Conclusions: The HEALING II study suggests that the EPC capture stent, aimed to stimulate the coronary vascular repair response, significantly promotes late regression of neointimal hyperplasia up to 18 months after stent implantation.

Stem/Progenitor-Cell-Based Approach for Restenosis after Percutaneous Coronary Intervention: Application of Bone Marrow Progenitors and Future Perspectives

“…+ EPC titers had lower rates of in-stent restenosis than patients with reduced circulating EPCs [39]. Intravascular ultrasound investigation in a subgroup analysis of this study demonstrated a regression of neointimal volume in patients with higher levels of EPCs.…”

Current concepts and new developments for autologous in vivo endothelialisation of biomaterials for intravascular applications

“…However, the titre of circulating CD34 + stem cells was elevated by only 12% (Garg et al, 2010), which shows that there is a discrepancy between the cells identified as EPCs and CD34 + cells. Probably, due to the failure of the therapy to augment CD34 + stem cell levels, (Duckers et al, 2007a) Patients on statins had more EPCs and less in-stent late loss than those not on statins in vivo (human) (HEALING IIB) (Garg et al, 2010) The pretreatment of patients with atorvastatin prior PCI had no benefit in terms of angiographic outcomes in vivo (human) TRIAS (Beijk et al, 2010) After In the randomised single-centre TRIAS (TRI-stent Adjudication Study) trial, the Genous TM stent was compared with a conventional drug eluting stent (DES) (the Taxus Liberté paclitaxel-eluting stent) in patients with de novo coronary lesions and a high-risk of coronary restenosis (Beijk et al, 2010). One year outcomes of the study showed that a subgroup of patients had a significantly higher late lumen loss in the Genous TM stent compared with the Taxus stent.…”

“…Numerous cytokines, growth factors, drugs and hormones, such as vascular endothelial growth factor (VEGF) (Asahara et al, 1999), angiopoietin-1, granulocyte colonystimulating factor (G-CSF), stromal cell-derived factor-1 (SDF-1) (Askari et al, 2003;Ceradini et al, 2004), erythropoietin (Heeschen et al, 2003), hepatocyte growth factor (HGF), oestrogen (Iwakura et al, 2003;Strehlow et al, 2003), and statins (Duckers et al, 2007b;Vasa et al, 2001a) induce the mobilisation of EPCs from the bone marrow into the circulating peripheral blood and can be used in vivo to boost the number of circulating EPCs in peripheral blood (Table 1). Furthermore, the ex vivo expansion of EPCs is often necessary for in vitro experiments or for potential clinical cell therapy of (Assmus et al, 2003), and PPAR-γ (Peroxisome Proliferator-Activated Receptor-γ) agonists (Gensch et al, 2007;Werner et al, 2007a), demonstrated the ability to stimulate the function of EPCs (Table 1).…”

“…The safety and feasibility of this stent was demonstrated in the single-centre HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) study (Aoki et al, 2005). Later, the efficacy of the Genous TM stent to prevent in-stent restenosis was evaluated (Silber, 2006;Duckers et al, 2007a;Duckers et al, 2007b;). In this multicentre HEALING II study, patients on statins had more EPCs and less in-stent late loss than those not on statins.…”

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles

“…Cardiac stem cells have been delivered to the heart as a possible treatment for myocardial infarction 4,5 . Vascular stents have been developed with CD34 antibodies to capture circulating progenitor cells 6 . While promising, these cell targeting approaches present drawbacks including lack of cell specificity, inconsistent cell retention, and off-target cell delivery.…”