Abstract
Metallic nanoparticles (NPs), as iron oxide NPs, accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Human stem cell-derived in vitro models may provide more realistic platforms to study NPs effects on neural cells, and to obtain relevant information on the potential for early or late DNT effects in humans. Primary neuronal-like cells (hNLCs) were generated from mesenchymal stem cells derived from human umbilical cord lining and the effects caused by magnetite (Fe3O4NPs, 1–50 μg/mL) evaluated. Neuronal differentiation process was divided into stages: undifferentiated, early, mid- and fully-differentiated (from day-2 to 8 of induction) based on different neuronal markers and morphological changes over time. Reduction in neuronal differentiation induction after NP exposure was observed associated with NP uptake: β-tubulin III (β-Tub III), microtubule-associated protein 2 (MAP-2), enolase (NSE) and nestin were downregulated (10–40%), starting from 25 μg/mL at the early stage. Effects were exacerbated at higher concentrations and persisted up to 8 days without cell morphology alterations. Adenosine triphosphate (ATP) and caspase-3/7 activity data indicated Fe3O4NPs-induced cell mortality in a concentration-dependent manner and increases of apoptosis: effects appeared early (from day-3), started at low concentrations (≥5 μg/mL) and persisted. This new human cell-based model allows different stages of hNLCs to be cultured, exposed to NPs/chemicals, and analyzed for different endpoints at early or later developmental stage.
Highlights
The toxicity of nanoparticles (NPs) is under continuous investigation to understand both the health impacts of atmospheric ultrafine particles and the safer use of engineered nanomaterials
Mesenchymal stem cell neurogenic potential was firstly assessed and the effects caused by Fe3O4NP exposure at T0 of the differentiation process were evaluated
cord lining membranes (CL)-hMSCs still showed the characteristic spindle-shaped morphology and formed a homogeneous monolayer typically belonging to mesenchymal stem cells
Summary
The toxicity of nanoparticles (NPs) is under continuous investigation to understand both the health impacts of atmospheric ultrafine particles and the safer use of engineered nanomaterials. Available evidence reports developmental toxicity of NPs due to their transfer from pregnant body to fetal circulation and offspring body including the developmental neurotoxicity (DNT). Regardless of the exposure route, NPs could reach the blood and translocate to brain. NPs distribution in the bloodstream raises a particular concern due to the potential NP transfer from placenta to the fetal central nervous system (CNS) and because blood-brain barrier (BBB) develops gradually in the fetal brain this type of direct exposure to NP in utero may have the most damaging consequences [1]. The transplacental diffusion of compounds from the mother to the offspring may be a cause of DNT. Several studies using different placental models, such as rodent and zebrafish (Danio rerio) embryogenesis models and perfusion models of the human placenta, demonstrated that NPs (i.e., Au, TiO2, SiO2, carbon, QD, and polystyrene NPs) can readily cross the placental barrier [2,3,4,5,6,7,8]
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