A bladder blueprint to build better models for understanding homeostasis and disease

Abstract

The bladder is a complex organ that can be affected by various pathologies, such as cancer or infection. It has a specific tissue structure composed of many different cell types and layers, including urothelial and endothelial cells but also a muscle layer controlling stretch and contraction to void urine. The bladder has constitutive and induced immune responses to infection or damage and harbours a microbiome. Each of these features can be influenced by factors including age and biological sex, which makes modelling homeostasis and disease in the bladder complex and challenging. To model diseases that affect the bladder, mouse models are an invaluable tool to understand the bladder in situ. However, stark differences exist between mice and humans, and so mouse models of human disease have limitations. Thus, models that more closely approximate human physiology would be expected to contribute to improved understanding of bladder biology. As technology advances, improvements in model development and creation of 3D bladder structures are enabling scientists to recapitulate essential aspects of human bladder physiology to gain increased understanding of bladder homeostasis and diseases. In this Review, the authors present the development, structure and microenvironment, and defence mechanisms of the bladder, which together create a blueprint that can be used to optimize current models or create new approaches.