Mesenchymal stromal cell labeling by new uncoated superparamagnetic maghemite nanoparticles in comparison with commercial Resovist - an initial in vitro study

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Authors

SKOPALÍK Josef POLAKOVA Katerina HAVRDOVA Marketa JUSTAN Ivan MAGRO Massimiliano MILDE David KNOPFOVÁ Lucia ŠMARDA Jan POLÁKOVÁ Helena GABRIELOVA Eva VIANELLO Fabio MICHÁLEK Jaroslav ZBORIL Radek

Year of publication 2014
Type Article in Periodical
Magazine / Source International Journal of Nanomedicine
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.2147/IJN.S66986
Field Pharmacology and pharmaceutical chemistry
Keywords mesenchymal stromal cells; stem cell tracking; magnetic resonance imaging; superparamagnetic iron oxide nanoparticles; stem cell labeling
Description Objective: Cell therapies have emerged as a promising approach in medicine. The basis of each therapy is the injection of 1-100x10(6) cells with regenerative potential into some part of the body. Mesenchymal stromal cells (MSCs) are the most used cell type in the cell therapy nowadays, but no gold standard for the labeling of the MSCs for magnetic resonance imaging (MRI) is available yet. This work evaluates our newly synthesized uncoated superparamagnetic maghemite nanoparticles (surface-active maghemite nanoparticles - SAMNs) as an MRI contrast intracellular probe usable in a clinical 1.5 T MRI system. Methods: MSCs from rat and human donors were isolated, and then incubated at different concentrations (10-200 mu g/mL) of SAMN maghemite nanoparticles for 48 hours. Viability, proliferation, and nanoparticle uptake efficiency were tested (using fluorescence microscopy, xCELLigence analysis, atomic absorption spectroscopy, and advanced microscopy techniques). Migration capacity, cluster of differentiation markers, effect of nanoparticles on long-term viability, contrast properties in MRI, and cocultivation of labeled cells with myocytes were also studied. Results: SAMNs do not affect MSC viability if the concentration does not exceed 100 mu g ferumoxide/mL, and this concentration does not alter their cell phenotype and long-term proliferation profile. After 48 hours of incubation, MSCs labeled with SAMNs show more than double the amount of iron per cell compared to Resovist-labeled cells, which correlates well with the better contrast properties of the SAMN cell sample in T2-weighted MRI. SAMN-labeled MSCs display strong adherence and excellent elasticity in a beating myocyte culture for a minimum of 7 days. Conclusion: Detailed in vitro tests and phantom tests on ex vivo tissue show that the new SAMNs are efficient MRI contrast agent probes with exclusive intracellular uptake and high biological safety.
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