Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders.

Current Challenges for Creating Meaningful Patient-Specific In Vitro Models to Study Brain DisordersA critical limitation of the field at present is the inherent difficulty in accurately defining cell states, particularly concerning the temporal and regional identity of pluripotent cells, neurons, and glial cells. A next step for hiPSC-based models of brain disorders will be building neural complexity in vitro, incorporating cell types and 3D organization to achieve network- and circuit-level structures. As the level of cellular complexity increases, new dimensions of modeling will emerge, and modeling neurological diseases that have a more complex etiology will be accessible. An important caveat to hiPSC-based models is the possibility that epigenetic factors and somatic mosaicism may contribute to neurological and neuropsychiatric disease, risk factors that may be difficult to capture in reprogramming or accurately recapitulate in vitro differentiation. A critical next step, in order to enable the use of hiPSCs for drug discovery, will be improving the scalability and reproducibility of in vitro differentiations and functional assays.

Banbury Meeting Attendees