title: Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.
abstract: Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS(-/-) mice ex and in vivo. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vosen
authors.forename: Sarah
authors.initials: S
authors.lastname: Rieck
authors.affiliation: Zentralinstitut für Medizintechnik (IMETUM), TU München , München 85748, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Heidsieck
authors.affiliation: Institute of Experimental Oncology and Therapy Research, TU München , München 81675, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne , Cologne 50735, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Physikalisch-Technische Bundesanstalt Berlin , Berlin 10587, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Eberbeck
authors.affiliation: Institute of Experimental Oncology and Therapy Research, TU München , München 81675, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.affiliation: Zentralinstitut für Medizintechnik (IMETUM), TU München , München 85748, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gleich
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D059346:Magnets; D051379:Mice; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D058185:Magnetite Nanoparticles; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: cell replacement; endothelial nitric oxide synthase (eNOS); endothelium; gene therapy; magnetic fields; magnetic nanoparticles; vascular function