Human neurospheres as three-dimensional cellular systems for developmental neurotoxicity testing.

BackgroundDevelopmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening.ObjectivesThe goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells.MethodsWe established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells.ResultsWe found that human neurospheres imitate proliferation, differentiatio...