Three-dimensional models for studying development and disease: moving on from organisms to organs-on-a-chip and organoids

Human development and disease are challenging to study because of lack of experimental accessibility to in vivo systems and the complex nature of biological processes. For these reasons researchers turn to the use of model systems, ranging in complexity and scale from single cells to model organisms. While the use of model organisms is valuable for studying physiology and pathophysiology in an in vivo context and for aiding pre-clinical development of therapeutics, animal models are costly, difficult to interrogate, and not always equivalent to human biology. For these reasons, three-dimensional (3D) cell cultures have emerged as an attractive model system that contains key aspects of in vivo tissue and organ complexity while being more experimentally tractable than model organisms. In particular, organ-on-a-chip and organoid models represent orthogonal approaches that have been able to recapitulate characteristics of physiology and disease. Here, we review advances in these two categories of 3D cultures and applications in studying development and disease. Additionally, we discuss development of key technologies that facilitate the generation of 3D cultures, including microfluidics, biomaterials, genome editing, and imaging technologies. Organ-on-a-chip and organoid culture models present complementary approaches in studying development and disease by balancing experimental tractability and the ability to mimic physiological complexity.