In conventional disease-modeling studies, cells are seeded in a two-dimensional plane. However, in vitro models with a 3D structure are closer to the physiological condition and thus may be better suited for the study of the disease pathology. Using disease-specific iPSCs, technologies for inducing the differentiation of several 3D structures, including those similar to the cortex, optic cup, Rathke’s pouch, cerebellum, and hippocampus, have been reported186–191. By taking advantage of the dynamic patterning and structural self-formation of complex organ buds, the construction of 3D structures and their corresponding networks has become a reality. Such a strategy is already being used in disease modeling for brain abnormalities117 and mental illness108. Similar to the self-organization of ectodermal tissue structures, endodermal tissue formation in 3D stem cell culture99 has been developed and applied to gastrointestinal disease modeling192. Physiological interactions among complex tissues from different lineages but with the same genetic background, such as the blood-brain barrier193 or the immune system194,195 within the organoid, could add new insights into normal physiology and diseases196,197.
