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SPIONs for cell labelling and tracking using MRI: magnetite or maghemite?

ABSTRACT: Although there is extensive literature covering the biomedical applications of superparamagnetic iron oxide nanoparticles (SPIONs), the phase of the iron oxide core used is not often taken into account when cell labelling and tracking studies for regenerative medicine are considered. Here, we use a co-precipitation reaction to synthesise particles of both magnetite- (Fe3O4) and maghemite- (?-Fe2O3) based cores and consider whether the extra synthesis step to make maghemite based particles is advantageous for cell tracking.

SUBMITTER: Barrow M

PROVIDER: S-EPMC5793703 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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SPIONs for cell labelling and tracking using MRI: magnetite or maghemite?

Barrow Michael M Taylor Arthur A Fuentes-Caparrós Ana M AM Sharkey Jack J Daniels Luke M LM Mandal Pranab P Park B Kevin BK Murray Patricia P Rosseinsky Matthew J MJ Adams Dave J DJ

Biomaterials science 20171201 1

Although there is extensive literature covering the biomedical applications of superparamagnetic iron oxide nanoparticles (SPIONs), the phase of the iron oxide core used is not often taken into account when cell labelling and tracking studies for regenerative medicine are considered. Here, we use a co-precipitation reaction to synthesise particles of both magnetite- (Fe3O4) and maghemite- (γ-Fe2O3) based cores and consider whether the extra synthesis s ...[more]

PMID: 29188240

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Project description:Background Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair. Purpose To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation. Results Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks. Conclusion Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sneag and Potter in this issue.

Project description:BackgroundArticular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells.Methodology/prinicipal findingsEfficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry.ConclusionsSPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.

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SPIONs for cell labelling and tracking using MRI: magnetite or maghemite?

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SPIONs for cell labelling and tracking using MRI: magnetite or maghemite?

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