Neurospheres for developmental neurotoxicity tests
2022
IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany
In this study, the neurosphere assay, a high-content assay for developmental neurotoxicity (DNT) evaluation, is scientifically validated using a mechanistic rationale approach. The neurosphere assay is based on human primary neural progenitor cells which are cultivated as neurospheres that have the potential to differentiate into brain effector cells including neurons, astrocytes and oligodendrocytes. The assay assesses the neurodevelopmental key events: progenitor cell proliferation, radial glia cell migration, neuronal differentiation, neurite outgrowth, oligodendrocyte differentiation, and thyroid hormone-dependent oligodendrocyte maturation.
A validation process was performed based on 1) describing the relevance of the respective endpoints for brain development, 2) the confirmation of the cell type-specific morphologies observed in vitro, 3) expressions of cell type-specific markers consistent with those morphologies, 4) appropriate anticipated responses to physiological pertinent signalling stimuli and 5) alterations in specific in vitro endpoints upon challenges with confirmed DNT compounds.
The results demonstrate that the neurosphere assay is suitable for DNT evaluation for regulatory purposes.
Scientific validation of human neurosphere assays for developmental neurotoxicity evaluation
Ellen Fritsche
Added on: 07-26-2022
[1] https://www.frontiersin.org/articles/10.3389/ftox.2022.816370/full
