Lung organoids: target cells for understanding respiratory diseases

Abstract

Human respiratory disease research currently lacks in vitro models that recapitulate most of the physiology and architecture of the lung. Furthermore, the complex composition and structure of the lung, as well as anatomical differences between humans and mice, frequently lead to disappointing results applied in vivo. Recent advances in organoid technology include new, sophisticated in vitro culture tools that have stimulated considerable interest due to their potential ability to functionally mimic the organ rather than two-dimensional culture or animal models. Hence, pluripotent stem cell-based organoid studies are emerging as an alternative approach able to recapitulate tissue architecture with remarkable fidelity. Moreover, these biomimetic tissue models can be used to investigate the mechanisms of progression of various diseases. Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are the most severe multifactorial respiratory disorders, characterized by irreversible airflow and progressive disease in elderly people. These diseases exhibit a progressive loss of alveolar type 2 epithelial (AT2) cells and accumulation of macrophages in the alveoli, leading to impaired pulmonary function. Despite recent advances in the study of COPD and IPF, effective treatments are lacking because our understanding of those diseases is hindered by their unknown mechanisms. Thus, in this review, the role of AT2 cells and macrophages is highlighted, along with their cell sources and applications for IPF and COPD modeling.