Although drug-eluting stents have dramatically reduced the recurrence of restenosis after vascular interventions, the nonselective antiproliferative drugs released from these devices significantly delay reendothelialization and vascular healing, increasing the risk of short- and long-term stent failure. Efficient repopulation of endothelial cells in the vessel wall following injury may limit complications, such as thrombosis, neoatherosclerosis, and restenosis, through reconstitution of a luminal barrier and cellular secretion of paracrine factors. We assessed the potential of magnetically mediated delivery of endothelial cells (ECs) to inhibit in-stent stenosis induced by mechanical injury in a rat carotid artery stent angioplasty model. ECs loaded with biodegradable superparamagnetic nanoparticles (MNPs) were administered at the distal end of the stented artery and localized to the stent using a brief exposure to a uniform magnetic field. After two months, magnetic localization of ECs demonstrated significant protection from stenosis at the distal part of the stent in the cell therapy group compared to both the proximal part of stent in the cell therapy group and the control (stented, nontreated) group: 1.7-fold (p < 0.001) less reduction in lumen diameter as measured by B-mode and color Doppler ultrasound, 2.3-fold (p < 0.001) less reduction in the ratios of peak systolic velocities as measured by pulsed wave Doppler ultrasound, and 2.1-fold (p < 0.001) attenuation of stenosis as determined through end point morphometric analysis. The study thus demonstrates that magnetically assisted delivery of ECs is a promising strategy for prevention of vessel lumen narrowing after stent angioplasty procedure.
OBJECTIVE: to demonstrate that systemically injected nanoparticles identify activated immune cells, which have been reported to accumulate in epileptogenic brain tissue.
BACKGROUND: Correct localization of epileptic foci can improve surgical outcome in patients with drug-resistant seizures.
DESIGN/METHODS: Fluorescent and magnetite-labeled nanoparticles were injected intravenously to rats with lithium-pilocarpine-induced chronic epilepsy. Cerebral uptake was studied ex vivo by confocal microscopy and MRI. The nanoparticles were also pre-loaded onto monocytes and injected to rats. Cellular uptake and biological effects were characterized in vitro in murine monocytes and microglia cell lines.
RESULTS: Microscopy confirmed that the nanoparticles selectively accumulate within myeloid cells in the hippocampus, in association with inflammation. The nanoparticle signal was also detectable by MRI. The in vitro studies demonstrate rapid nanoparticle uptake and good cellular tolerability. Injection of nanoparticle-loaded monocytes improved the nanoparticle optical detection.
CONCLUSIONS: We show that nanoparticles can target myeloid cells in epileptogenic brain tissue. This system can contribute to pre-surgical and intra-surgical localization of epileptic foci, and assist in detecting immune system involvement in epilepsy.
Study Supported by: Drexel-IDR Translational Research Partnership, the Israel Ministry of Industry and Trade (Kamin; 520008095 and 510424534), the Louis and Bessie Stein Family foundation through the Drexel University College of Medicine, USA Award Number 5R01HL107771 from the National Heart, Lung and Blood Institute, the Brettler Centre for Research in Molecular Pharmacology and Therapeutics, and Prusiner-Abramsky Awards in Basic Clinical Neuroscience. Disclosure: Dr. Eyal has nothing to disclose. Dr. Portnoy has nothing to disclose. Dr. Polyak has nothing to disclose. Dr. Inbar has nothing to disclose. Dr. Kenan has nothing to disclose. Dr. Rai has nothing to disclose. Dr. Wehrli has nothing to disclose. Dr. Bishara has nothing to disclose. Dr. Mann has nothing to disclose. Dr. Shmuel has nothing to disclose. Dr. Itzhak has nothing to disclose. Dr. Ben Hur has nothing to disclose. Dr. Ekstein has nothing to disclose.
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