Next‐generation preclinical models of lung development, physiology and disease

Abstract

The incidence of respiratory diseases such as chronic obstructive pulmonary disease and pulmonary cancer is growing significantly around the world, making pulmonary disease one of the leading causes of mortality. However, the development of effective therapeutics for pulmonary diseases has been hindered by the lack of human-mimetic physiological models that reliably emulate patient responses. Recent advances in technology and cell culture have led to the development of organoids and organ-on-a-chip models that allow us to recapitulate the structure, cellular organization, and organ-level responses of the target tissue in vitro. Here, we review the advances and milestones of lung organoid and lung-on-a-chip models in the past decade and highlight their applications in mimicking pulmonary system development, physiology, disease, and regeneration. In addition, we discuss the ongoing challenges and the future prospects of integrating lung organoids and lung-on-a-chip models to overcome current limitations and to enhance their physiological relevance. These human-centric models are likely to provide important insights into pulmonary physiology and pathophysiology for drug discovery that complement and potentially replace traditional animal models.

A vascularized crypt-patterned colon model for high-throughput drug screening and disease modelling

“…These factors ultimately limit transferability of preclinical results to human clinical trial responses. 11,12 To better emulate human physiology, recent studies have focused on human colon organoids derived from primary colon resident stem cells or isolated primary crypts seeded into hydrogel scaffolds such as Matrigel domes. [13][14][15][16] These multicellular constructs, usually 100-200 μm in diameter, can recapitulate in vivo colon form and function through crypt budding, differentiation and cell renewal.…”