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Advances in Human Lung Disease Models: Stem Cell-based Platforms for Modeling Airway and Alveolar Disease
Journal article   Open access   Peer reviewed

Advances in Human Lung Disease Models: Stem Cell-based Platforms for Modeling Airway and Alveolar Disease

Daniel J Wallman, Sinem Koc-Gunel, Robert E Hynds, Amy L Ryan and Ruth Olmer
American journal of physiology. Lung cellular and molecular physiology, Vol.331(1), pp.L48-L56
07/2026
DOI: 10.1152/ajplung.00092.2026
PMID: 42222930
url
https://doi.org/10.1152/ajplung.00092.2026View
Published (Version of record) Open Access

Abstract

This minireview, inspired by the 20th 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.
 Stem Cells Regeneration Alveolar Airway Lung Disease

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