Human-Induced Pluripotent Stem Cell-Derived Neural Organoids as a Novel In Vitro Platform for Developmental Neurotoxicity Assessment

There has been a recent drive to replace in vivo studies with in vitro studies in the field of toxicity testing. Therefore, instead of conventional animal or planar cell culture models, there is an urgent need for in vitro systems whose conditions can be strictly controlled, including cell-cell interactions and sensitivity to low doses of chemicals. Neural organoids generated from human-induced pluripotent stem cells (iPSCs) are a promising in vitro platform for modeling human brain development. In this study, we developed a new tool based on various iPSCs to study and predict chemical-induced toxicity in humans. The model displayed several neurodevelopmental features and showed good reproducibility, comparable to that of previously published models. The results revealed that basic fibroblast growth factor plays a key role in the formation of the embryoid body, as well as complex neural networks and higher-order structures such as layered stacking. Using organoid models, pesticide toxicities were assessed. Cells treated with low concentrations of rotenone underwent apoptosis to a greater extent than those treated with high concentrations of rotenone. Morphological changes associated with the development of neural progenitor cells were observed after exposure to low doses of chlorpyrifos. These findings suggest that the neuronal organoids developed in this study mimic the developmental processes occurring in the brain and nerves and are a useful tool for evaluating drug efficacy, safety, and toxicity.