Lung organoid models

The application of organoid models to understand lung development, study disease, and investigate regeneration has grown rapidly over the past decade. Formation of more complex multicellular and three-dimensional lung structures provides an environment that is hoped to more closely resemble a physiological in vivo microenvironment when compared to more traditional two-dimensional (2D) models. Protocols were originally generated for the culture of primary lung tissues, either from the developing lung creating organoids to study lung development and branching morphogenesis or from adult lung tissue studying proximal and distal lung spheroids in the context of health and disease. Recent optimization of these methods has enabled the differentiation and expansion of pluripotent stem cell–derived airway epithelial stem cells, including basal cells and alveolar type 2 cells. Models can both mimic human lung development and aspects of human lung physiology and pathophysiology, allowing the ability to ask questions that are not readily testable in 2D culture systems. Over the next few years, it can be expected that these technologies will continue to evolve, methods for analysis will improve, and our capacity to model complex human lung disease will significantly advance. This chapter focuses on discussion of the technological advances that have been made to study mouse and human organoids, primary and pluripotent stem cell–derived cells, and models of human lung diseases.