Assessment of neurotoxicity of pharmacological compounds during early neural development of human embryonic stem cells.

Human embryonic stem cells (hESCs), with the potential for differentiation, have been used to evaluate the embryotoxicity of various compounds. The effects of pharmacological compounds (cytosine arabinoside, 5-fluorouracil, hydroxyurea, indomethacin, and dexamethasone) on neurogenesis of hESCs over 28 days were examined based on cytotoxicity (half-maximal inhibitory concentration of viability, IC50 ) and expression of neural markers. Cytosine arabinoside, 5-fluorouracil, and hydroxyurea showed strong cytotoxicity (IC50 < 10 μM), whereas indomethacin and dexamethasone had weaker cytotoxic effects. Dose-dependent expression profiles of neural markers in the compound-treated groups are presented in triangular charts to allow comparison with the standard expression levels in the control group. Differences in compound-specific reductions in expression patterns of GAD1, OLIG2, FABP, and NES were similar to the differences in cytotoxic strength. Cytosine arabinoside diminished nestin and β3-tubulin in neural differentiated hESCs. The results of this study extend the understanding of how differentiated hESCs may be useful for assessment of cell viability or neurogenesis impairment by chemicals that could have effects during the embryonic stage, particularly during neurogenesis.