Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

Abstract

Magnetic nanoparticles (NPs), such as very small iron oxide NPs (VSOPs) can be used for targeted drug delivery, cancer treatment or tissue engineering. Another important field of application is the labelling of mesenchymal stem cells to allow in vivo tracking and visualization of transplanted cells using magnetic resonance imaging (MRI). For these NPs, however, various toxic effects, as well as functional impairment of the exposed cells, are described. The present study evaluates the influence of VSOPs on the multilineage differentiation ability and cytokine secretion of human adipose tissue derived stromal cells (hASCs) after long-term exposure. Human ASCs were labelled with VSOPs, and the efficacy of the labelling was documented over 4 weeks in vitro cultivation of the labelled cells. Unlabelled hASCs served as negative controls. Four weeks after labelling, adipogenic and osteogenic differentiation was histologically evaluated and quantified by polymerase chain reaction (PCR). Changes in gene expression of IL-6, IL-8, VEGF and caspase 3 were determined over 4 weeks. Four weeks after the labelling procedure, labelled and unlabelled hASCs did not differ in the gene expression of IL-6, IL-8, VEGF and caspase 3. Furthermore, the labelling procedure had no influence on the multidifferentiation ability of hASC. The percentage of labelled cells decreased during in vitro expansion over 4 weeks. Labelling with VSOPs and long-term intracellular disposition probably have no influence on the physiological functions of hASCs. This could be important for the future in vivo use of iron oxide NPs.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles

“…In-vitro labeling of human adipose tissue derived from stromal cells with VSOPs shows no influence on the physiological function of the cells. Preclinical in-vivo characterization in pigs and mice confirmed a good tolerance and safety profile (Wagner et al, 2002;Radeloff et al, 2020). Preliminary studies done by Wagner et al measured a LD 50 (lethal dose) in mice of >17.9 mmol Fe per kg of body weight (Wagner et al, 2002).…”

Superparamagnetic Iron Oxide Particles (VSOPs) Show Genotoxic Effects but No Functional Impact on Human Adipose Tissue-Derived Stromal Cells (ASCs)

“…In a recently published study of our own group using the same VSOPs for long-term analyses, the dynamic light scattering obtained a z-average hydrodynamical diameter of 16.47 nm, and a polydispersity index of 0.282 was yielded. The zeta potential at pH 7.4 was −28 mV with an isoelectric point of 3.2 [ 55 ]. The information on relaxivity of VSOPs C200 was taken from the publication of Stroh et al [ 39 ]: R1 22.5 mmol −1 s −1 at 0.47 T and R2 49.7 mmol −1 s −1 at 0.47.…”

“…The intracellular particle distribution and accumulation of VSOPs was visualized by transmission electron microscopy (TEM), as described previously [ 55 , 57 ]. VSOPs-labeled and unlabeled hASCs were fixed in 0.1 M sodium cacodylate buffer (pH 7.2) with 2.5% glutaraldehyde and 2% formaldehyde.…”

Hope for bone regeneration: The versatility of iron oxide nanoparticles

“…Superparamagnetic iron oxide nanoparticles (SPIONs) are a type of IONPs with a diameter of 10–100 nm and can generate strong magnetism in a weak magnetic field, and its magnetism can disappear with the withdrawal of the external magnetic field ( Laurent et al, 2008 ; Kircher et al, 2011 ). Based on its superparamagnetic properties, IONPs are usually used in MRI examinations and targeted to specific areas under the action of an external magnetic field to achieve targeted therapeutic effects ( Radeloff et al, 2020 ). Maria et al ( Volokhova et al 2022) made SiO 2 -coated magnetic iron oxide nanoparticles into α-Fe@SiO 2 with a cubic morphology, which exhibited higher MRI relaxation than iron oxide alone and could show high-performance contrast effects.…”