Abstract 2034: Magnetic Cell Targeting to Stented Arteries
Introduction: In-stent restenosis is a major complication of coronary stenting. Although gene therapeutic approaches addressing this problem showed promise, the inability to localize the gene vector to the injured vessel compromises their clinical use. We hypothesized that genetically altered cells could be made magnetically responsive through loading with super-paramagnetic nanoparticles (MNP) and that these cells could then be delivered to stented arteries via applied magnetic field gradients.
Methods: Rat endothelial cells were loaded with fluorescently labeled biodegradable MNP. Fluorimetry and fluorescent microscopy were used to determine the effect of experimental variables on loading efficiency and uptake rate, as well as cell capture on magnetizable 304 stainless steel (SS) stents in a model circulation system under a uniform magnetic field (1000 G). Cell viability was determined by the AlamarBlue assay. Magnetic cell targeting to balloon injured rat carotid arteries with deployed 304 SS stents (with or without a local uniform magnetic field) was assayed by bioluminescence 3 days after local delivery of MNP-loaded cells transduced with luciferase encoding adenovirus (lucAd). Additionally magnetic targeting to a stented carotid artery after systemic delivery via cell injection into the left ventricle was examined by fluorescent microscopy.
Results: The rate and extent of MNP cellular uptake under a magnetic field (500 G) depended directly on the MNP dose resulting in ~1 ng MNP/cell within 24 hr without adversely affecting cell viability (>90% compared to untreated cells). Magnetically responsive cells displayed first order capture kinetics on 304 SS stent with an initial capture rate of 1% per min in model in vitro experiments. A proof of concept in vivo experiment with local delivery of lucAd-transduced cells to stented arteries showed high expression of luciferase 3 days post treatment. Intraventricular injection of MNP-loaded cells resulted in a significantly higher number of cells localized per magnetic targeting to deployed stents compared to a ‘no field’ control.
Conclusion: This study demonstrates the feasibility of magnetic targeting of genetically modified cells as a potential therapeutic strategy for in-stent restenosis.