title: Mesenchymal stromal cell labeling by new uncoated superparamagnetic maghemite nanoparticles in comparison with commercial Resovist--an initial in vitro study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Masaryk University, Brno, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Skopalik
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Polakova
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Havrdova
authors.affiliation: Department of Pharmacology, Masaryk University, Brno, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Justan
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Magro
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: David
authors.initials: D
authors.lastname: Milde
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Knopfova
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Smarda
authors.affiliation: Department of Pharmacology, Masaryk University, Brno, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Polakova
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Gabrielova
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic ; Department of Comparative Biomedicine and Food Science, University of Padua, Padova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Vianello
authors.affiliation: Department of Pharmacology, Masaryk University, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Michalek
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry and Analytical Chemistry, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Zboril
mesh_terms: D000818:Animals; D002468:Cell Physiological Phenomena / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D003911:Dextrans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides
keywords: magnetic resonance imaging; mesenchymal stromal cells; stem cell labeling; stem cell tracking; superparamagnetic iron oxide nanoparticles