Three-dimensional platforms of human induced pluripotent stem cell (hiPSC)-derived neurons enable greater physiological relevance and promise to breathe new life into drug discovery programs. A fundamental requirement of this re-vitalization is high-throughput and informative interrogation methodologies.StemoniX has developed microBrain®3D, ready to use spheroids comprised of human iPSC-derived cortical neurons and astrocytes supplied in ready to use 96- and 384-well plates.Real-time, high-throughput kinetic imaging has demonstrated the value of this preparation in functional screening and disease model settings while advancements in tissue clearing and spheroid processing are enabling in-depth, granular structural examinations. In particular, our data demonstrate a dramatic benefit of tissue clearing for confocal analysis of neuronal spheroids stained with antibodies and Cell Painting dyes as well as enhanced throughput enabled by physical stabilization of spheroids on flat-bottom imaging plates. This presentation will highlight recent uses of microBrain 3D in functional 384-well based screens, patient-derived disease models, phenotypic rescue, and image-based interrogation. Together 3D human neural spheroids with functional and structural experimental methodologies hold the potential to overcome several bottlenecks in CNS-based drug discovery.
