Developmental Neurotoxicity Assessment in Stem Cell Models

Developmental neurotoxicity assessment in stem cell models has emerged as a transformative discipline, aiming to detect and characterise chemical or drug-induced disruptions in human neurodevelopment without reliance on animal testing. Central to this approach are human induced pluripotent stem cells (hiPSCs) and neural progenitor cells, which can be directed to differentiate into key neural lineages and form three-dimensional structures resembling aspects of the developing brain. These systems reproduce fundamental processes such as cell proliferation, migration, differentiation and synaptogenesis, enabling quantification of adverse effects at defined stages. A major objective is to assemble batteries of complementary assays—each probing distinct neurodevelopmental events—into integrated testing strategies. Coupled with high-content imaging, transcriptomics and metabolomics, such batteries facilitate mechanistic insight and prediction of hazard potency. In parallel, the adverse outcome pathway (AOP) framework provides a structured means to link molecular initiating events to higher-order neurological deficits, guiding assay selection and interpretation of in vitro findings. Advances in biokinetic modelling and cheminformatics further support extrapolation from in vitro concentrations to human exposure scenarios, paving the way for next-generation risk assessment that is both human-relevant and scalable to thousands of untested compounds.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Developmental Neurotoxicity Assessment in Stem Cell Models publication trend

The graph below shows the total number of articles in developmental neurotoxicity assessment in stem cell models across all publications each year (not limited to Nature Index journals).

Technical terms

hiPSC: Human induced pluripotent stem cell, a reprogrammed somatic cell capable of differentiating into any cell type, including neural lineages.

Neural crest cell: A multipotent progenitor cell originating at the dorsal neural tube that migrates and differentiates into diverse cell types in the peripheral nervous system.

Adverse outcome pathway (AOP): A structured representation linking a molecular initiating event through key biological changes to an adverse health effect.

New approach methodology (NAM): Any non-animal technique, including in vitro, in silico or alternative organism models, used for hazard identification and risk assessment.

DNT in vitro battery: A curated set of complementary cell-based assays designed to assess distinct neurodevelopmental processes affected by toxicants.

References

1. Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing. Archives of Toxicology (2024).
2. Inhibition of Neural Crest Cell Migration by Strobilurin Fungicides and Other Mitochondrial Toxicants. Cells (2024).
3. Strategies to improve the regulatory assessment of developmental neurotoxicity (DNT) using in vitro methods. Toxicology and Applied Pharmacology (2018).