Dataset Information

Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model.

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.

SUBMITTER: Larsen K

PROVIDER: S-EPMC3249218 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Publications

Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model.

Larsen Katarína K Cheng Caroline C Tempel Dennie D Parker Sherry S Yazdani Saami S den Dekker Wijnand K WK Houtgraaf Jaco H JH de Jong Renate R Swager-ten Hoor Stijn S Ligtenberg Erik E Hanson Stephen R SR Rowland Steve S Kolodgie Frank F Serruys Patrick W PW Virmani Renu R Duckers Henricus J HJ

European heart journal 20110706 1

<h4>Aims</h4>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.<h4>Methods and results</h4>First, 15 patients undergoing coronary angiography received an extracorporeal femoral arteriovenous (AV) shu ...[more]

PMID: 21733913

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Project description:AimsInteratrial shunting (IAS) reduces left atrial pressure in patients with heart failure. Several clinical trials reported that IAS improved the New York Heart Association score and exercise capacity. However, its effects on haemodynamics vary depending on shunt size, cardiovascular properties, and stressed blood volume. To maximize the benefit of IAS, quantitative prediction of haemodynamics under IAS in individual patients is essential. The generalized circulatory equilibrium framework determines circulatory equilibrium as the intersection of the cardiac output curve and the venous return surface. By incorporating IAS into the framework, we predict the impact of IAS on haemodynamics.Methods and resultsIn seven mongrel dogs, we ligated the left anterior descending artery and created impaired cardiac function with elevated left atrial pressure (baseline: 7.8 ± 1.0 vs. impaired: 11.9 ± 3.2 mmHg). We established extracorporeal left-to-right atrial shunting with a centrifugal pump. After recording pre-IAS haemodynamics, we changed IAS flow stepwise to various levels and measured haemodynamics under IAS. To predict the impact of IAS on haemodynamics, we modelled the fluid mechanics of IAS by Newton's second law and incorporated IAS into the generalized circulatory equilibrium framework. Using pre-IAS haemodynamic data obtained from the dogs, we predicted the impact of IAS flow on haemodynamics under IAS condition using a set of equations. We compared the predicted haemodynamic data with those measured. The predicted pulmonary flow [r2 = 0.88, root mean squared error (RMSE) 11.4 mL/min/kg, P < 0.001), systemic flow (r2 = 0.92, RMSE 11.2 mL/min/kg, P < 0.001), right atrial pressure (r2 = 0.92, RMSE 0.71 mmHg, P < 0.001), and left atrial pressure (r2 = 0.83, RMSE 0.95 mmHg, P < 0.001) matched well with those measured under normal and impaired cardiac function. Using this framework, we further performed a simulation study to examine the haemodynamic benefit of IAS in heart failure with preserved ejection fraction. We simulated the IAS haemodynamics under volume loading and exercise conditions. Volume loading and exercise markedly increased left atrial pressure. IAS size-dependently attenuated the increase in left atrial pressure in both volume loading and exercise. These results indicate that IAS improves volume and exercise intolerance.ConclusionsThe framework developed in this study quantitatively predicts the haemodynamic impact of IAS. Simulation study elucidates how IAS improve haemodynamics under volume loading and exercise conditions. Quantitative prediction of IAS haemodynamics would contribute to maximizing the benefit of IAS in patients with heart failure.

Dataset Information

Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model.

Aims

Methods and results

Conclusion

Publications

Capture of circulatory endothelial progenitor cells and accelerated re-endothelialization of a bio-engineered stent in human ex vivo shunt and rabbit denudation model.

Similar Datasets

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