Neural Progenitor Cell Derivation Methodologies for Drug Discovery Applications

Inducible pluripotent stem cells (iPSCs) are being used to model brain disorders across the continuum of neurodevelopment, neurodegenerative, and neuropsychiatric disease allowing for the mechanistic unraveling of the neurological disease state. Subsequently, there is a diverse array of cell model systems that can be used for target validation, pharmacodynamic endpoint development, and high-throughput/content assay development and screening. However, to successfully model neurological disorders with iPSCs, the disease-relevant neuron must be first identified, and it is critical to have the appropriate neuronal progenitor cell derivation and neuron differentiation protocols available to produce desired neuronal phenotypes. Moreover, special considerations are necessary if adaptation to high-throughput/content assay systems is anticipated. Discussed here are the three-dimensional embryoid body-neural rosette and two-dimensional monolayer methodologies to derive iPS neural progenitor cells and neurons with a specific focus on cortical neurons. Outlined are some of the commonalities, advantages, and disadvantages associated with both methodologies.