Lung organoids as emerging models in idiopathic pulmonary fibrosis research: Current applications, challenges, and future directions

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with progressive, irreversible scarring and a median survival of approximately 3–5 years after diagnosis. Current therapies (nintedanib, pirfenidone) modestly slow progression but do not halt or reverse fibrosis, creating a critical therapeutic plateau and unmet need. Improved human-centric models are essential to dissect how genetic susceptibility and chronic epithelial exhaustion drive aberrant repair in IPF. Lung organoids, as three-dimensional (3D) constructs that recapitulate human lung architecture and cellular responses to pathological cues have increasingly been used as important human-relevant platforms for IPF research. In this review, we summarize recent advances in the application of lung organoids to IPF research, including disease modeling, mechanistic studies, and preclinical drug testing, and we discuss the potential and current limitations of patient-derived organoids (PDOs) in personalized medicine. We also outline ongoing efforts to improve these models through the incorporation of vascular, immune, and mechanical components, such as assembloids and lung-on-a-chip systems. Although important challenges remain, including maturation, standardization, and scalability, lung organoids may provide a valuable complementary platform for future IPF research and translational studies.