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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Differentiating human NT2/D1 neurospheres as a versatile in vitro 3D model system for developmental neurotoxicity
E J Hill1, E K Woehrling, M Prince
1School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, UK. hillej@aston.ac.uk
Toxicology
|July 5, 2008
Summary
This study tested teratogens on differentiating NT2/D1 cells to identify developmental neurotoxins. Valproic acid significantly impacted neurogenesis, showing its potential as a developmental neurotoxin in this in vitro model.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Developmental neurotoxicity poses significant human health risks with potential long-term neurological consequences.
- Identifying specific developmental neurotoxins is crucial for understanding and mitigating these risks.
Purpose of the Study:
- To evaluate the utility of a Ntera2/clone D1 (NT2/D1) cell neurosphere model for identifying developmental neurotoxins.
- To assess the impact of known human teratogens on neurogenesis in vitro.
Main Methods:
- Differentiating NT2/D1 cell neurospheres were exposed to teratogens classified by the European Centre for the Validation of Alternative Methods (ECVAM).
- Endpoints assessed included cell viability and the expression of central nervous system-specific neuronal protein markers.
Main Results:
- Valproic acid demonstrated the most significant negative effect on neurogenesis, reducing viability and neuronal markers.
- Hydroxyurea and acrylamide reduced cell viability but did not impact neuronal marker expression.
- Lithium exhibited minimal effects on cell viability and neuronal marker expression.
Conclusions:
- The NT2/D1 neurosphere model shows promise as an in vitro system for assessing developmental neurotoxicity.
- Valproic acid emerged as a potent developmental neurotoxin within this model, affecting neurogenesis.
- Further validation is needed, but the model may aid in identifying environmental or chemical threats to neurodevelopment.
