Magnetic Nanoparticle-Mediated Targeting of Cell Therapy Reduces In-Stent Stenosis in Injured Arteries.

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.

Functional behavior and gene expression of magnetic nanoparticle-loaded primary endothelial cells for targeting vascular stents.

AIM: To assess functional competence and gene expression of magnetic nanoparticle (MNP)-loaded primary endothelial cells (ECs) as potential cell-based therapy vectors. MATERIALS & METHODS: A quantitative tube formation, nitric oxide and adhesion assays were conducted to assess functional potency of the MNP-loaded ECs. A quantitative real-time PCR was used to profile genes in both MNP-loaded at static conditions and in vitro targeted ECs. RESULTS: Functional behavior of MNP-loaded and unloaded cells was comparable. MNPs induce expression of genes involved in EC growth and survival, while repress genes involved in coagulation. CONCLUSION: MNPs do not adversely affect cellular function. Gene expression indicates that targeting MNP-loaded ECs to vascular stents may potentially stimulate re-endothelialization of an implant and attenuate neointimal hyperplasia.