Endothelial Progenitor Cell Seeded Self-Expanding Vascular Stent

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DESCRIPTION (provided by applicant): Objectives: It is the goal of this study to develop a technology to line self-expanding Nitinol stents with autologous peripheral blood-derived endothelial progenitor cells (EPCs) in order to reduce the common and potentially devastating complications of in-stent restenosis and thrombosis. Nitinol stents are used to treat narrowing of blood vessels in patients with peripheral vascular disease, an illness that will affect over 20 million patients in the U.S. by 2020. Aims and Methods: It is our Aim I in this study to optimize a novel technology to seed Nitinol stents with EPCs derived from peripheral blood and to evaluate EPC function on the stent surface ex vivo. We plan on manufacturing an innovative Nitinol delivery system that allows seeding the stents within minutes of implantation by laser drilling micropores in the outside stent sheath so that EPCs can be seeded on the inside strut surface by using the principle of solvent drag when forcing EPC-containing solution through a stent side- port. We will also optimize stent imaging and re-compressing methods. In Aim I.B. we will assess cell retention on Nitinol stents under physiological shear stress in an ex vivo flow circuit and test whether adhesion is mediated by cell wall phosphoproteins. In Aim I.C. we evaluate nitric oxide production by quantifying nitrite in media samples with an Ionics/Sievers Nitric Oxide Analyzer and thrombomodulin expression by EPCs on the stent surface with Western blot analysis under different flow conditions. In Aim 2, we will test EPC-coated Nitinol stents in a porcine animal model. Aim 2.A. will allow us to test our novel methods of seeding Nitinol stents with fluorescently-labeled EPCs and implanting them into 3 pilot animals in a short-term survival study. Following, in Aim 2.B. we will implant one EPC-coated and one uncoated (control) stent into the right and left external jugular vein of 7 pigs. The differences in thrombosis and restenosis between treated and control stents will be evaluated by histomorphometric semiquantitative analyses, as well as scanning- and fluorescent microscopy. Impact: The knowledge gained in this proposal will deepen our understanding of the function and adhesion mechanism of EPCs on Nitinol under shear stress. If successful, we will have provided proof-of-concept for a novel technology, which will significantly improve the performance of self-expanding stents and may benefit millions of patients.