title: Superparamagnetic iron oxide nanoparticles as a means to track mesenchymal stem cells in a large animal model of tendon injury.
abstract: The goal of this study was to establish an SPIO-based cell-tracking method in an ovine model of tendonitis and to determine if this method may be useful for further study of cellular therapies in tendonitis in vivo. Functional assays were performed on labeled and unlabeled cells to ensure that no significant changes were induced by intracellular SPIOs. Following biosafety validation, tendon lesions were mechanically (n = 4) or chemically (n = 4) induced in four sheep and scanned ex vivo at 7 and 14 days to determine the presence and distribution of intralesional cells. Ovine MSCs labeled with 50 µg SPIOs/mL remained viable, proliferate, and undergo tri-lineage differentiation (p < 0.05). Labeled ovine MSCs remained detectable in vitro in concentrated cell numbers as low as 10 000 and in volumetric distributions as low as 100 000 cells/mL. Cells remained detectable by MRI at 7 days, as confirmed by correlative histology for dually labeled SPIO+/GFP+ cells. Histological evidence at 14 days suggested that SPIO particles remained embedded in tissue, providing MRI signal, although cells were no longer present. SPIO labeling has proven to be an effective method for cell tracking for a large animal model of tendon injury for up to 7 days post-injection. The data obtained in this study justify further investigation into the effects of MSC survival and migration on overall tendon healing and tissue regeneration.
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, H-322, Athens, GA, 30602, USA.|Department of Biological and Agricultural Engineering, College of Engineering, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scharf
authors.affiliation: Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Holmes
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, H-322, Athens, GA, 30602, USA.
authors.forename: Merrilee
authors.initials: M
authors.lastname: Thoresen
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, H-322, Athens, GA, 30602, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mumaw
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, H-322, Athens, GA, 30602, USA.
authors.forename: Alaina
authors.initials: A
authors.lastname: Stumpf
authors.affiliation: Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, H-322, Athens, GA, 30602, USA.
authors.forename: John
authors.initials: J
authors.lastname: Peroni
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D012756:Sheep; D013708:Tendon Injuries / Q000473:pathology*
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide
keywords: MRI; MSC; SPIO; cell tracking