Spontaneous Epileptic Recordings from hiPSC-Derived Cortical Neurons Cultured with a Human Epileptic Brain Biopsy on a Multi Electrode Array

Abstract

A growing societal awareness is calling upon scientists to reconsider the use of animals in research, which stimulates the development of translational in vitro models. The physiological and architectural interactions between different cell types within an organ present a challenge to these models, particularly for a complex organ such as the brain. Thus far, in vitro brain models mostly consist of a single cell type and demonstrate little predictive value. Here, we present a co-culture of an epileptic human neocortical biopsy on a layer of human induced pluripotent stem cell (hiPSC)-derived cortical neurons. The activity of the cortical neurons was recorded by a 120-electrode multi-electrode array. Recordings were obtained at 0, 3, and 6 days after assembly and compared to those obtained from cortical neurons without a biopsy. On all three recording days, the hybrid model displayed a firing rate, burst behavior, number of isolated spikes, inter-spike interval, and network bursting pattern that aligns with the characteristics of an epileptic network as reported by others. Thus, this novel model may be a non-animal, translational alternative for testing new therapies up to six days after resection.