title: FMN-coated fluorescent USPIO for cell labeling and non-invasive MR imaging in tissue engineering.
abstract: Non-invasive magnetic resonance imaging (MRI) is gaining significant attention in the field of tissue engineering, since it can provide valuable information on in vitro production parameters and in vivo performance. It can e.g. be used to monitor the morphology, location and function of the regenerated tissue, the integrity, remodeling and resorption of the scaffold, and the fate of the implanted cells. Since cells are not visible using conventional MR techniques, ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are routinely employed to label and monitor the cells embedded in tissue-engineered implants. We here set out to optimize cell labeling procedures with regard to labeling efficiency, biocompatibility and in vitro validation during bioreactor cultivation, using flavin mononucleotide (FMN)-coated fluorescent USPIO (FLUSPIO). Efficient FLUSPIO uptake is demonstrated in three different cell lines, applying relatively short incubation times and low labeling concentrations. FLUSPIO-labeled cells were successfully employed to visualize collagen scaffolds and tissue-engineered vascular grafts. Besides promoting safe and efficient cell uptake, an exquisite property of the non-polymeric FMN-coating is that it renders the USPIO fluorescent, providing a means for in vitro, in vivo and ex vivo validation via fluorescence microscopy and fluorescence reflectance imaging (FRI). FLUSPIO cell labeling is consequently considered to be a suitable tool for theranostic tissue engineering purposes.
authors.affiliation: 1. Department of Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany;
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Mertens
authors.affiliation: 2. Department of Tissue Engineering & Textile Implants, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Frese
authors.affiliation: 1. Department of Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany;
authors.forename: Deniz Ali
authors.initials: DA
authors.lastname: Bölükbas
authors.affiliation: 2. Department of Tissue Engineering & Textile Implants, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Hrdlicka
authors.affiliation: 1. Department of Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany;
authors.forename: Susanne
authors.initials: S
authors.lastname: Golombek
authors.affiliation: 2. Department of Tissue Engineering & Textile Implants, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Koch
authors.affiliation: 2. Department of Tissue Engineering & Textile Implants, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Mela
authors.affiliation: 2. Department of Tissue Engineering & Textile Implants, Applied Medical Engineering, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhövel
authors.affiliation: 1. Department of Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: 1. Department of Experimental Molecular Imaging, Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany;
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D049109:Cell Proliferation; D058948:Cell Tracking / Q000379:methods*; D003911:Dextrans / Q000737:chemistry*; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D041681:NIH 3T3 Cells; D061848:Optical Imaging; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C097921:ferumoxtran-10; D005486:Flavin Mononucleotide
keywords: FLUSPIO; MRI; tissue engineering