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

J. Skopalik, K. Polakova, M. Havrdova, I. Justan, M. Magro, D. Milde, L. Knopfova, J. Smarda, H. Polakova, E. Gabrielova, F. Vianello, J. Michalek, R. Zboril,

. 2014 ; 9 (-) : 5355-72. [pub] 20141120

Language English Country New Zealand

Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15031605

OBJECTIVE: Cell therapies have emerged as a promising approach in medicine. The basis of each therapy is the injection of 1-100×10(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 μg/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 μg 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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$a OBJECTIVE: Cell therapies have emerged as a promising approach in medicine. The basis of each therapy is the injection of 1-100×10(6) cells with regenerative potential into some part of the body. Mesenchymal stromal cells (MSCs) are the most used cell type in the cell therapy nowadays, but no gold standard for the labeling of the MSCs for magnetic resonance imaging (MRI) is available yet. This work evaluates our newly synthesized uncoated superparamagnetic maghemite nanoparticles (surface-active maghemite nanoparticles - SAMNs) as an MRI contrast intracellular probe usable in a clinical 1.5 T MRI system. METHODS: MSCs from rat and human donors were isolated, and then incubated at different concentrations (10-200 μg/mL) of SAMN maghemite nanoparticles for 48 hours. Viability, proliferation, and nanoparticle uptake efficiency were tested (using fluorescence microscopy, xCELLigence analysis, atomic absorption spectroscopy, and advanced microscopy techniques). Migration capacity, cluster of differentiation markers, effect of nanoparticles on long-term viability, contrast properties in MRI, and cocultivation of labeled cells with myocytes were also studied. RESULTS: SAMNs do not affect MSC viability if the concentration does not exceed 100 μg ferumoxide/mL, and this concentration does not alter their cell phenotype and long-term proliferation profile. After 48 hours of incubation, MSCs labeled with SAMNs show more than double the amount of iron per cell compared to Resovist-labeled cells, which correlates well with the better contrast properties of the SAMN cell sample in T2-weighted MRI. SAMN-labeled MSCs display strong adherence and excellent elasticity in a beating myocyte culture for a minimum of 7 days. CONCLUSION: Detailed in vitro tests and phantom tests on ex vivo tissue show that the new SAMNs are efficient MRI contrast agent probes with exclusive intracellular uptake and high biological safety.
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$a Polakova, Katerina $u Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
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$a Justan, Ivan $u Department of Pharmacology, Masaryk University, Brno, Czech Republic.
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$a Magro, Massimiliano $u Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy.
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$a Milde, David $u Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
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$a Smarda, Jan $u Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
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$a Gabrielova, Eva $u Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
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$a Michalek, Jaroslav $u Department of Pharmacology, Masaryk University, Brno, Czech Republic.
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