Human induced pluripotent stem cells (iPSCs) technology is expected to provide a new human cell-based platform to overcome the species difference. In our previous study, we have established screening system of chemicals/drugs to prioritize them for developmental neurotoxicity (DNT) potential using iPSCs and iPSC-neurons. Benzodiazepines are widely used for anxiety, insomnia and epileptic seizure. An increased risk of congenital malformations and other developmental abnormalities associated with the use of benzodiazepine drugs during pregnancy has been suggested. In the present study, we evaluated diazepam using neural differentiation process (structural toxicity) using iPSCs and electrophysiological properties (functional toxicity) using iPSC-derived neurons. Diazepam reduced the expression of Pax6, a marker of neurogenesis and decreased ATP levels in iPSCs. In addition, diazepam reduced the number of spikes and network burst neurons using iPSC-derived neurons recorded by multi-electrode array system.
Taken together, our data suggest that iPSCs and iPSC-derived neurons are useful for integrated safety assessment.