Human induced pluripotent stem cells for in vitro modeling of impaired mucociliary clearance in cystic fibrosis lung disease

• CF iPSC-derived airway cultures (iALI) closely recapitulate primary airway cultures in gene expression, ultrastructure, and CFTR function, providing a robust in vitro model of CF lung disease. • A novel, sensitive, and automatable ciliary beat frequency (CBF) assay overcomes limitations of conventional assays and directly reflects impaired mucociliary clearance in CF. • Electron microscopy confirmed the CF disease phenotype, showing a dense and dehydrated mucus layer on iALI cultures, validating the model's pathophysiological relevance. • CFTR modulator drugs partially rescued the disease phenotype in iALI cultures, demonstrating the platform's utility for personalized drug testing and development.