Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells

Abstract

Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 µg/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.

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

“…Information on the influence of IONPs exposition and their intracellular accumulation on the functional capabilities of hASCs is still incomplete and partially controversial [14,43,44]. Our study group previously demonstrated the intracellular accumulation and persistence of ZnO-NPs in hASCs after long-term cultivation [34,45]. Exposure of ZnO-NPs affected cell migration of hASCs [46], but not their ability to multidifferentiate [34,46].…”

“…Our study group previously demonstrated the intracellular accumulation and persistence of ZnO-NPs in hASCs after long-term cultivation [34,45]. Exposure of ZnO-NPs affected cell migration of hASCs [46], but not their ability to multidifferentiate [34,46]. The present study was conducted to add information on the effect of citrate-coated VSOPs on hASCs.…”

“…In order to quantify VSOPs-containing cells in culture and to determine the intracellular distribution of VSOPs, TEM analysis was performed, as described previously [32][33][34]. VSOPs-labelled and unlabelled hASCs from three patients were used as pellets 24 h after the labelling procedure and after 7, 14, 21 and 28 days for these analyses.…”

Combined Dextran-Graft-Polyacrylamide/Zinc Oxide Nanocarrier for Effective Anticancer Therapy in vitro

“…53 On the other hand, subtoxic concentrations of ZnO NPs did not affect cytokine secretion and differentiation of human adipose tissue-derived stromal cells. 54 Toxic effects on isolated mice bone marrow mesenchymal stem cells were observed with ZnO NPs of 6-8 nm in size, leading to mitochondrial and cytoskeletal disturbances and increased ROS generation at concentrations above 20 mg/mL. 55 The cytotoxicity of ZnO NPs is known to be dependent on their size.…”

The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing Is Associated with Oxidative Stress In Vitro

“…The ZnO-NP were previously characterized by our group [17,18]. Transmission electron microscopy (TEM) (Zeiss transmission electron microscope EM 900, Carl Zeiss, Oberkochen, Germany) was used to assess particle size distribution and morphology at the Division of Electron Microscopy at the Biocenter of University of Würzburg.…”