The interactions between different cell types can be better modeled using 3D organoids. Organoids have been generated for multiple organs, including the brain, retina, intestine, kidney, liver, lung, and stomach, using both tissue stem cells and pluripotent stem cells from mice and humans97. Human iPSC-derived organoids have been developed for a variety of applications due to their resemblance to endogenous cell organization and organ structure, and are particularly useful because they allow the possibility to study cell-cell interactions in a cellular context that mimics human physiology and development. The 3D organoids have been used in modeling human organ development and diseases, testing therapeutic compounds, and cell transplantation98–114 (Table 4). Multiple cell types that are physiologically relevant can be generated in organoids following a spatial-temporal order. Moreover, cells generated in organoids can be functionally more mature than cells derived using directed differentiation protocols, due to the interaction of different cell types, such as neurons and astrocytes, in the 3D structure. Therefore, 3D organoids allow dissection of disease pathology in a developmentally relevant spatial-temporal context and have the potential to offer a drug response at the level of an organ, rather than at the level of individual cells.
