Seeding endothelial progenitor cells on a self-expanding metal stent: an in vitro study.
ABSTRACT To demonstrate the feasibility of seeding a self-expanding metal stent with endothelial progenitor cells to enhance rapid reendothelialization, which is postulated to prevent local thrombus formation and restenosis after vascular intervention.
Endothelial progenitor cells and fibrinogen were isolated from the peripheral blood of a domestic swine and then cultured and identified. Ten self-expanding nitinol stents were incubated in the culture medium with a cell concentration of 1 x 10(6)/mL with (n = 5, study group) or without (n = 5, control group) fibrin gel (5 mg/mL fibrinogen and 0.10 NIHU/mL thrombin) for 24 hours. The cell coverage of the stents was documented with en face photography and scanning electron microscopy. After simulated use in vitro, the cells were removed from each stent, counted with a cytometer, sequentially cultured for three passages, and identified again to compare their properties with those of the original seeding line.
After seeding the stent with the combination of endothelial progenitor cells and the fibrin gel coating, the stents took on a tube-like appearance with a confluent monolayer membrane. After digestion with trypsin, a mean of 2.5 x 10(5) +/- 1.3 cells were obtained from the fibrin gel stent (study group); fewer cells (4 x 10(4) +/- 1.5) were recovered from the bare stents (control group) (P < .01). The recovered cells, after amplification with culture, demonstrated the properties of the original endothelial progenitor cells.
An endothelial progenitor cell-coated stent can be successfully fabricated by using fibrin gel as the bonding agent in vitro. Further in vivo research is warranted.
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ABSTRACT: Rapid re-endothelialization at an atherosclerotic lesion after balloon inflation or stent deployment may be essential for reducing or preventing local thrombus formation and restenosis. In order to prevent these complications via enhanced rapid re-endothelialization, we fabricated two types of endothelial progenitor cell (EPC)-seeded intravascular stent devices. One was a photocured gelatin-coated metallic stent, and the other was a microporous thin segmented polyurethane (SPU) film-covered stent on which photocured gelatin was coated. Both devices were seeded with ex vivo expanded EPCs obtained from canine peripheral blood. Seeded EPCs formed confluent monolayers onto surfaces of both photocured gelatin-coated stent struts and SPU film, and a majority of cells remained on surfaces of stents after stent expansion. The EPC-seeded stent was expanded in a tubular hybrid vascular medial tissue composed of vascular smooth muscle cells and collagen as an arterial media mimic. After 7-day culture, EPCs, which migrated from the stent struts, proliferated and endothelialized the luminal surfaces of the hybrid vascular medial tissue. This in vitro pilot study prior to in vivo experiments suggests that on-stent cell delivery of EPCs may be novel therapeutic devices for re-endothelialization or endothelium lining or paving at an atherosclerotic arterial wall, resulting in the prevention of on-stent thrombus formation and in-stent restenosis, as well as the rapid formation of normal tissue architecture.Biomaterials 07/2003; 24(13):2295-302. · 7.60 Impact Factor
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ABSTRACT: To prospectively evaluate the outcome with circulating endothelial progenitor cell (EPC) capture stent implantation in a cohort of consecutive patients with high-risk angiographic and/or clinical features. Genous R-stent is a stainless steel coronary stent covered with antibodies specific to EPC's surface antigens, designed to promote the formation of a confluent functional endothelial layer over the device; conceivably, this may prevent both stent thrombosis and restenosis. From November 2005 to March 2007, 80 patients received 93 EPC capture stents at Campus Bio-Medico, University of Rome. Patients had two or more of the following high-risk features: diabetes mellitus (33%), unstable coronary syndromes (73%), left ventricular dysfunction (8%), multivessel intervention (9%), B2/C lesions (56%). Acute success was achieved in 79/80 patients (98%), without Q-wave myocardial infarction (MI), in-hospital death or emergency bypass surgery; no patient had acute or subacute stent thrombosis. Follow-up was available in 78 patients (mean 14 +/- 4 months): noncardiac death occurred in one patient, acute MI in one patient; no patient required bypass surgery; 10 patients (13%) underwent percutaneous target lesion revascularization (TLR); three patients (4%) had reintervention on a nontarget vessel. Kaplan-Meyer life-table analysis showed event-free survival of 86% and TLR-free survival of 90% at one and a half year follow-up. The cell capture stent is safe and effective, with satisfactory immediate results and mid-term outcome, without evidence of stent thrombosis. Whether those devices represent a viable alternative to currently available drug-eluting or bare metal stents will need to be evaluated in larger randomized studies.Catheterization and Cardiovascular Interventions 05/2008; 71(5):600-4. · 2.51 Impact Factor
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ABSTRACT: Drug-eluting stents for coronary artery disease results in inhibition of smooth muscle cell (SMC) and endothelial cells which may increase the risk of stent thrombosis. In this study, we attempted to enhance re-endothelialization of deployed stents while simultaneously inhibiting intimal hyperplasia by overexpression of endothelial nitric oxide synthase (eNOS) delivery in the vasculature using an adenovirus gene-eluting stent. Re-endothelialization was significantly greater in vessels obtained from normocholesterolemic animals at day 14 (85.34% +/- 7.38 versus 62.66% +/- 10.49; P < 0.05) and day 28 (91.1% +/- 10 versus 63.1% +/- 22; P < 0.05) and hypercholesterolemic animals (96.97% +/- 3.2 versus 28.33% +/- 38.76; P < 0.05) at day 28 with AdeNOS-eluting stents. At day 28, there was a significant increase in the lumen size [AdeNOS 2.73 mm(2) +/- 1.18, AdbetaGal 0.98 mm(2) +/- 0.98, phosphorylcholine (PC) 1.87 mm(2) +/- 1.18; P < 0.05], and a significant reduction in neointimal formation (AdeNOS 2.32 mm(2) +/- 1.13, AdbetaGal 3.73 mm(2) +/- 0.95, PC 3.2 mm(2) +/- 0.94; P < 0.05), and percent restenosis (AdeNOS 45.23 +/- 20.81, AdbetaGal 79.6 +/- 20.31, PC 70.16 +/- 22.2; P < 0.05) in AdeNOS-stented vessels in comparison with controls from hypercholesterolemic animals, assessed by morphometry and quantitative coronary angiography (AdeNOS 15.95% +/- 7.63, AdbetaGal 56.9% +/- 38.6, PC 58 +/- 34.6; P < 0.05). Stent-based delivery of AdeNOS results in enhanced endothelial regeneration and reduction in neointimal formation as compared with controls. This seems to be a promising treatment strategy for preventing in-stent restenosis (ISR) while simultaneously reducing the risk of stent thrombosis.Molecular Therapy 09/2008; 16(10):1674-80. · 7.04 Impact Factor