This minireview, inspired by the 20 th Anniversary Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases conference, summarizes two decades of advances in human-specific lung disease modeling. We discuss endogenous stem cell-based platforms for both distal alveolar and proximal airway epithelia, including primary alveolar type II cell, bronchial and nasal epithelial cultures established as organoids, air-liquid interface cultures and ex vivo preparations. Advances in iPSC-derived basal and alveolar epithelial cells, humanized graft models and high-throughput therapeutic screening are highlighted. Collectively, these in vitro and in vivo models are transforming the study of lung development, injury, and repair, while accelerating drug discovery and regenerative medicine strategies. Finally, we emphasize the critical need for integrating immune components into organotypic cultures and for establishing rigorous validation and benchmarking standards to maximize translational relevance.
Wallman et al. (Mon,) studied this question.