Modeling the human Brain-on-Chip with human iPSC-derived Glutamatergic neurons

There is an urgent need for translational preclinical models to enhance successful clinical trials outcomes particularly for neurological troubles innovative therapeutics. Alternative methods, such as predictive human based in vitro models, are particularly in the spotlight of Regulatory Bodies. Organs-on-Chips (OoCs) are hence considered as particularly relevant to reduce the need, cost and ethical burden of animal studies. Such models are based both on the relevance of the cells used and the ability to build precise, yet physiologically relevant, complex architectures. Human induced pluripotent stem cells (hiPSCs) derived neurons are now considered as the gold standard. 

Brain-on-Chip is the creation of humanized neural networks culture in relevant microfluidic architectures that mimics the human brain organization with the possibility to analyze specific readouts. Adoption by the pharmaceutical industry of OoC models requires the establishment of standardized and normalized cell culture conditions and validation criteria.

Here, we present data characterizing NETRI’s Brain-on Chip with BrainXell’s hiPSC-derived neurons as a relevant minimalist model of the human brain recapitulating morphological and functional characteristics of human brain tissue. Our methodology is:
•Use of reproducible and characterized mature human neurons.

•Standardization of microfluidic quality control.

•Establishment of Standard Operating Procedure (SOP) for culture and maintenance human neurons in microfluidic devices.