Table 1.

Comparison of current major seizure-liability testing models with proposed iPSC-derived model.

Model	Benefits	Limitations
Acute slice assay	simple • Representative of in vivo rodent adult brain simple • Same day experimentation simple • Validated for use simple • Defined cytoarchitecture simple • Current ‘gold standard’ simple • Forms functional network	simple • Difficulty in inter-species extrapolation simple • Preparations undergo cellular changes and damage simple • Projection neurons severed simple • Typically low throughput
Organotypic slice culture	simple • Representative of in vivo rodent simple • Retain connective properties of the tissue simple • Can recover from damage from slicing simple • Can assess long-term effects of neuroactive chemicals simple • Forms functional network	simple • Difficulty in inter-species extrapolation simple • Derived from neonates, so may not be predictive of matured system simple • More time consuming simple • Requires supportive culture medium simple • Synaptic reorganization/remodeling
Primary CNS culture	simple • Representative of cell subtypes in vivo simple • Predictive model validated simple • Higher throughput than slices	simple • Difficulty in inter-species extrapolation simple • Loss of structure and 3-dimensionality simple • More time consuming simple • Do cultured cells reach maturity? simple • Often cultured in absence of astrocytes or other neural cells
iPSC-derived culture	simple • Human-based simple • Exhibit humanoid morphology simple • Retain genotype of original fibroblast, so can be used to model genetic components of epilepsy from patients with specific mutations simple • Amenable to increased throughput simple • No ethical considerations	simple • Expensive simple • Time consuming simple • Research still in infancy, lacking validation simple • No defined ultrastructure simple • No guarantee of presence of desired cell types simple • No standard protocol