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Chakraborty, A. ; Zöller, M. ; Sardogan, A. ; Klotz, M. ; Mastalerz, M. ; Marchi, H. ; Meixner, R. ; Hatz, R.A.* ; Behr, J.* ; Hilgendorff, A. ; Nakayama, M. ; Staab-Weijnitz, C.A.

Development of a polidocanol-based human in vitro model to explore airway epithelial repair.

Am. J. Respir. Cell Mol. Biol. 73, 668-685 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The human airway epithelium is a primary site of toxicant exposure and crucial in the pathogenesis of acute and chronic lung disease (CLD). In CLD, the airway epithelium is frequently altered and distorted, and its restoration is desirable. The mechanisms underlying human aberrant epithelial regeneration, however, are poorly understood. Importantly, our knowledge about airway epithelial injury and regeneration largely stems from mouse models, yet airways differ considerably between mice and humans. We hypothesized that treatment of differentiated primary human bronchial epithelial cells (phBECs, or HBEC) with polidocanol or naphthalene would allow for studying mechanisms of human airway epithelial injury and regeneration. Injury of differentiated phBECs with 0.04%, but not 0.1% PDOC, resulted in full restoration of a functional epithelium and epithelial barrier integrity as monitored by qRT-PCR analysis, immunofluorescence stainings, and transepithelial electrical resistance measurements. Regeneration was associated with a transient but not parallel increase of p21+ and KRT17+ cells. Providing proof-of-concept, DAPT, an inhibitor of Notch signaling, blunted the restoration of secretory cell types post 0.04% PDOC injury. Differentiation of phBECs in presence of cigarette smoke extract (CSE) or ethanol as first hit significantly impaired the regeneration capacity of phBECs. While naphthalene is known to specifically induce club cell depletion in mouse airways, it failed to do so in phBECs. In conclusion, using fully differentiated phBECs treated with PDOC, we successfully established and thoroughly characterized a human in vitro system that will facilitate studies of mechanisms involved in susceptibility to injury as well as human airway repair and regeneration.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Airway Injury ; Airway Regeneration ; Bronchial Epithelium ; Hbec ; Polidocanol; Pulmonary Neuroendocrine Cells; Gene-transfer; Basal-cells; Lung Development; Clara Cells; Stem-cells; Naphthalene; Activation; Mouse; Regeneration
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Journal American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Volume: 73, Issue: 5, Pages: 668-685 Article Number: , Supplement: ,
Publisher American Thoracic Society
Publishing Place 25 Broadway, 18 Fl, New York, Ny 10004 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Regenerative Biology and Medicine (IRBM)
CF Statistical Consulting (CF-STATCON)
Grants CPC Research School "Lung Biology and Disease"
German Center for Lung Research (DZL)
Helmholtz Association
German Research Foundation (Deutsche Forschungsgemeinschaft)
Federal Institute for Risk Assessment (Bundesinstitut fur Risikobewertung)