Best Practices for Translational Disease Modeling Using Human IPSC-Derived Neurons

From the beginning, induced pluripotent stem cell (iPSC) technology was touted as a path to improve our understanding of disease biology and enable drug discovery. Advances in iPSC culture, genome engineering, and differentiation protocols have rapidly expanded the use of iPSC-derived disease models from the specialized work of stem cell biology into the mainstream toolkit of cellular neuroscience. Here we provide guidance for using iPSC-derived neurons for disease modeling with a focus on enabling screening platforms amenable to therapeutic drug discovery. We also highlight the potential for incorporating three-dimensional systems that may create more translational in vitro models.