In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining

Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe(3)O(4)NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe(3)O(4)NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3O4NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 mu g/mL in CL-MSCs and 100 mu g/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 mu g/mL); (2) cell density decrease and monolayer features loss were affected at >= 50 mu g/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 mu g/mL Fe3O4NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe(3)O(4)NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3O4NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.