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A Khurana, H Nejadnik, F Chapelin, O Lenkov, R Gawande, S Lee, SN Gupta, N Aflakian, N Derugin, S Messing, G Lin, TF Lue, L Pisani and HE Daldrup-Link
Abstract
Aim: To develop a clinically applicable MRI technique for tracking stem cells in matrix-associated stem-cell implants, using the US FDA-approved iron supplement ferumoxytol. Materials & methods: Ferumoxytol-labeling of adipose-derived stem cells (ADSCs) was optimized in vitro. A total of 11 rats with osteochondral defects of both femurs were implanted with ferumoxytol- or ferumoxides-labeled or unlabeled ADSCs, and underwent MRI up to 4 weeks post matrix-associated stem-cell implant. The signal-to-noise ratio of different matrix-associated stem-cell implant was compared with t-tests and correlated with histopathology. Results: An incubation concentration of 500 µg iron/ml ferumoxytol and 10 µg/ml protamine sulfate led to significant cellular iron uptake, T2 signal effects and unimpaired ADSC viability. In vivo, ferumoxytol- and ferumoxides-labeled ADSCs demonstrated significantly lower signal-to-noise ratio values compared with unlabeled controls (p < 0.01). Histopathology confirmed engraftment of labeled ADSCs, with slow dilution of the iron label over time. Conclusion: Ferumoxytol can be used for in vivo tracking of stem cells with MRI. Original submitted 28 February 2012; Revised submitted 8 November 2012.
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Concepts
Iron, Leukemia inhibitory factor, Signal-to-noise ratio, Cell division, Inner cell mass, Stem cell, In vivo, In vitro
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