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. 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.

Quantitative Magnetic Particle Imaging Monitors the Transplantation, Biodistribution, and Clearance of Stem Cells In Vivo

“…For hMSC populations (n = 3) labeled using 20, 30, and 40 μg Fe/mL Resovist labeling concentrations respectively, MPI imaging indicated iron uptake of 50.8 ± 12.0, 55.8 ± 10.9, and 85.7 ± 20.7 pg Fe/cell, and ICP analysis showed good agreement with MPI measurements (R 2 = 0.89) with intracellular iron measurements of 44.2 ± 11.1, 53.9 ± 11.8, and 77.8 ± 23.3 pg Fe/cell. These intracellular uptake values are in agreement with published data for Resovist labeling of MSCs 23 - 25 , 34 , 35 . An MTT viability assay showed no significant difference in cell viability between unlabeled and labeled hMSC populations (Fig.…”

The surface reactivity of iron oxide nanoparticles as a potential hazard for aquatic environments: A study on Daphnia magna adults and embryos

“…In recent years, SAMNs were proposed for biotechnological applications and their cytotoxicity was extensively studied in vitro on eukaryotic cells, such as HeLa cells 40 , mesenchymal stromal cells (MSCs) from rat and human 39 , mesenchymal stem cells from horse peripheral blood 42 and on prokaryotic cells, such as Salmonella typhimurium 60 and Pseudomonas fluorescens 46 . This body of work laid the basis for moving to an animal model.…”

“…Surface Active Maghemite Nanoparticles (SAMNs) stand out among iron oxide nanomaterials for their exceptional colloidal stability in the absence of any coating or surface modifier, leading to excellent cellular uptake 39 , low toxicity 40 , excellent contrast agent properties for magnetic resonance imaging (MRI) 41 , and their application as magnetic carriers for biomolecules 42 . These unusual characteristics can be usefully applied to deepen our knowledge on the effects of metal oxide nanomaterials on biological systems, without any interference by organic or inorganic shells.…”

Nanoparticle strategies for cancer therapeutics: Nucleic acids, polyamines, bovine serum amine oxidase and iron oxide nanoparticles (Review)

“…non-toxicity, biodegradability, and biocompatibility) that justify their role in drug delivery. The ability of iron oxide nanoparticles to undergo cellular phagocytosis facilitates their use in contrast enhanced MRI beyond vascular and tissue morphology imaging (111), thereby enabling novel applications of iron oxide nanoparticles for MRI based diagnosis of liver diseases, cancer metastasis to lymph nodes, and in vivo tracking of implanted cells and grafts. Functionalized and engineered magnetic nanoparticles have been developed to meet the increasing demand for non-invasive in vivo imaging of molecular and cellular activities, specific to a disease state.…”