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Beyond the Epithelium: Multicellular Niches in Lung Regeneration and Disease
Journal article   Open access   Peer reviewed

Beyond the Epithelium: Multicellular Niches in Lung Regeneration and Disease

Sinem Koc-Gunel, Amy L Ryan, Rob E Hynds and Jaymin J Kathiriya
American journal of physiology. Lung cellular and molecular physiology, Vol.330(6), pp.L770-L779
06/2026
DOI: 10.1152/ajplung.00419.2025
PMID: 42059862
url
https://doi.org/10.1152/ajplung.00419.2025View
Published (Version of record) Open Access

Abstract

Pulmonary homeostasis and regeneration require coordination between epithelial cells, immune populations, vascular networks, extracellular matrix, and stromal cells. This mini review examines recent advances in lung niche biology that were a focus of the 2025 Stem Cells, Cell Therapy and Bioengineering in Lung Biology and Diseases Conference. Here we emphasize the impact of non-epithelial compartments essential for tissue function and repair. Reflecting the conference's emphasis on comprehensive niche biology, we highlight how non-epithelial compartments, including stromal, vascular, and immune cells, serve as essential regulators of tissue function and repair, a perspective that unified many of the presentations and discussions. In diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease, disruption of these niche interactions, rather than isolated cellular defects, drives regenerative failure. Spatial transcriptomic approaches reveal how pathological cell states colocalize within aberrant micro-niches. These insights suggest that effective therapeutics must target entire multicellular ecosystems, with advanced organoid platforms offering promising tools for developing niche-modulating interventions.
 Extracellular Matrix Stem Cells Mechanosensing Micro-niches Airway

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