Organotypic Airway Models Derived from Primary Human Nasal Epithelial Cells

The respiratory system is essential for gas exchange and immune defense but is highly susceptible to pathogens and harmful agents. Chronic rhinosinusitis, asthma, COPD, and emerging viral infections represent a global health burden. As the first line of defense, the nasal epithelium plays a central role in respiratory health. Understanding its structural and functional changes is critical for clarifying immune responses and disease mechanisms. This review summarizes recent advances in human nasal epithelial cell (hNEC) models and their applications in respiratory research.

Submerged cultures are simple and suitable for basic assays but lack complexity, whereas air-liquid interface (ALI) cultures allow hNECs to differentiate into physiologically relevant models to preserve native epithelial signatures. It can be integrated with immune co-cultures to capture disease-specific inflammation, and are sensitive to culture expansion methods, underscoring the need for standardization. Patient-derived hNECs are increasingly used to investigate infection dynamics and provide mechanistic insight, while new apical-out organoid systems enable direct access to the epithelial surface, enhancing studies of differentiation, remodeling, and host-pathogen interactions. Nasal epithelial models, especially ALI cultures and organoids, provide powerful tools for investigating respiratory disease mechanisms and guiding therapeutic development.