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.

Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration

“…In a study, IONPs labeled BMSCs were implanted into skull defects of Sprague‐Dawley rats, the labeled cells were effectively tracked in vivo by MRI, and histological examination and statistical analysis indicated that IONPs labeling did not affect the viability or differentiation ability of BMSCs . IONPs‐based MSCs‐tracking was also attempted to implement in a sheep ovine model of tendonitis and the labeled cells remained detectable by MRI at 7 days . Furthermore, Nedopil et al.…”

Use of contrast media in computed tomography and magnetic resonance imaging in horses: Techniques, adverse events and opportunities

“…As with all metal-based contrast media, dissociation of the metal ion from the bound complex or leakage from a nanoparticle leads to toxicity [273,274]. Superparamagnetic nanoparticles are used to label mesenchymal stem cells for equine DDFT lesion assessment [276]. Classified as superparamagnetic (>50 nm) and ultrasmall superparamagnetic (<50 nm) iron oxide [215], they can also be coated with liposomes, dextran, etc.…”

Nanotechnology for mesenchymal stem cell therapies

“…Although not developed for stem cell-based applications SPIONs have been quickly adapted for tracking stem cells post implantation [128]. They have been successfully used to track MSC in rat [129,130], equine [131], porcine [132,133], ovine [134], canine [135] in vivo models.…”