Functional Behavior and Gene Expression of Magnetic Nanoparticle-Loaded Primary Endothelial Cells for Targeting Vascular Stents

Zohra, Fatema Tuj; Medved, Mikhail; Lazareva, Nina; Polyak, Boris

doi:10.2217/nnm.15.13

Cited by 16 publications

(11 citation statements)

References 52 publications

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“…This did not markedly affect cell functional competence, gene expression, intracellular organelles, or cell respiration. 44,45 The results from our previous study demonstrated the feasibility of magnetic guidance to target (model) ECs to stented rat carotids mediated by a uniform magnetic field. ECs administered into the left ventricular cavity via intracardiac injection were uniformly captured from systemic circulation onto the stent struts.…”

Section: Discussionmentioning

confidence: 92%

“…Therefore, the current therapeutic efficacy study was conducted using inbred Lewis rats and syngeneic primary aortic ECs isolated from closely related individuals. The syngeneic cells used in this study represented a highly pure culture of ECs (98% CD31 + , 90% Tie-2 + , and 4% α-SMA − (SMA = smooth muscle actin) per flow cytometry) 44 that were tolerated well by all the recipient animals. It is noteworthy that the internalization of polymeric MNPs used in this study to confer cells with magnetic responsiveness for achieving efficient targeting was accomplished by loading an individual cell on average with ∼25 pg of magnetite.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Typically this may be with an external magnet34 but increasingly magnetic implants are being developed, as in the orthopaedic field where insertion of magnetic scaffolds with or without permanent magnets can be used to aid healing of massive bone defects and chondro-osseous defects353637, or in vascular surgery where magnetic stents can aid targeting of magnetised endothelial cells38. The assimilation of magnetic nanoparticle synthesis into mammalian cells creates a real and compelling, cytocompatible, alternative to exogenous administration of SPIONs.…”

Section: Discussionmentioning

confidence: 99%

Biosynthesis of magnetic nanoparticles by human mesenchymal stem cells following transfection with the magnetotactic bacterial gene mms6

Elfick

Rischitor

Mouras

et al. 2017

Sci Rep

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The use of stem cells to support tissue repair is facilitated by loading of the therapeutic cells with magnetic nanoparticles (MNPs) enabling magnetic tracking and targeting. Current methods for magnetizing cells use artificial MNPs and have disadvantages of variable uptake, cellular cytotoxicity and loss of nanoparticles on cell division. Here we demonstrate a transgenic approach to magnetize human mesenchymal stem cells (MSCs). MSCs are genetically modified by transfection with the mms6 gene derived from Magnetospirillum magneticum AMB-1, a magnetotactic bacterium that synthesises single-magnetic domain crystals which are incorporated into magnetosomes. Following transfection of MSCs with the mms6 gene there is bio-assimilated synthesis of intracytoplasmic magnetic nanoparticles which can be imaged by MR and which have no deleterious effects on cell proliferation, migration or differentiation. The assimilation of magnetic nanoparticle synthesis into mammalian cells creates a real and compelling, cytocompatible, alternative to exogenous administration of MNPs.

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“…Biodegradable PLGA-magnetite SPIONs provided an effective and safe means for cell labeling at lower levels of iron loading. 27 PLGA is an FDA-approved polymer and has been used for over 30 years for intracellular drug delivery. [28][29][30][31] In vivo degradation is well documented and can be controlled by molecular weight, crystallinity, ratio of lactide:glycolide, and nanoparticle size.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent

Tefft

Uthamaraj

Harbuzariu

et al. 2018

Tissue Engineering Part A

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Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic cell capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (FeO) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled cells to 2205 SS stents. In this study, we show extensive endothelialization of magnetic 2205 SS stents (median 98.4% cell coverage) within 3 days, whereas the control 316L SS stents exhibited significantly less coverage (median 48.9% cell coverage, p < 0.0001). This demonstrates the ability of intracoronary delivery of magnetic nanoparticle labeled autologous endothelial cells to improve endothelialization of magnetized coronary stents within 3 days of implantation.

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Functional Behavior and Gene Expression of Magnetic Nanoparticle-Loaded Primary Endothelial Cells for Targeting Vascular Stents

Cited by 16 publications

References 52 publications

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

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

Biosynthesis of magnetic nanoparticles by human mesenchymal stem cells following transfection with the magnetotactic bacterial gene mms6

Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent

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