A practical toolbox for modelling fibrosis in vitro

Abstract

Fibrosis is a widespread disease implicated in millions of deaths worldwide and impacting diverse organs, including the heart, lung, kidney, liver and synovium. Characterized by excessive extracellular matrix deposition, fibrosis leads to tissue scarring and dysfunction, ultimately resulting in organ failure. The development of faithful experimental models of fibrosis is challenged by its complexity, limiting the discovery of effective therapeutics. Human in vitro tissue models are emerging as powerful systems that capture the pathophysiology of fibrosis to uncover disease mechanisms, identify biomarkers and facilitate drug discovery. Here we define the hallmarks of fibrosis across organ systems to establish foundational design criteria necessary for modelling human fibrosis in vitro. We provide an overview of state-of-the-art technologies and recent advancements in tissue fibrosis models pointing towards potential future directions. Finally, we offer a practical toolkit for researchers with diverse expertise to implement these considerations into future tissue models. Key tissue features shared by fibrotic diseases are distilled into clear design rules for human in vitro models, with practical guidance on choosing cells, matrices and platforms for mechanistic studies and drug testing.