Three-dimensional organotypic culture: experimental models of mammalian biology and disease

Recent advances in three-dimensional (3D) culture techniques have increased our understanding of the cellular mechanisms that drive epithelial tissue development, the genetic regulation of cell behaviours in epithelial tissues and the role of microenvironmental factors in normal development and disease. 3D culture can be used to build complex organs and to advance therapeutic approaches. Mammalian organs are challenging to study as they are fairly inaccessible to experimental manipulation and optical observation. Recent advances in three-dimensional (3D) culture techniques, coupled with the ability to independently manipulate genetic and microenvironmental factors, have enabled the real-time study of mammalian tissues. These systems have been used to visualize the cellular basis of epithelial morphogenesis, to test the roles of specific genes in regulating cell behaviours within epithelial tissues and to elucidate the contribution of microenvironmental factors to normal and disease processes. Collectively, these novel models can be used to answer fundamental biological questions and generate replacement human tissues, and they enable testing of novel therapeutic approaches, often using patient-derived cells.