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Nawroth, J. ; Roth, D.* ; van Schadewijk, A.* ; Ravi, A.* ; Maulana, T.I.* ; Senger, C.N.* ; van Riet, S.* ; Ninaber, D.K.* ; de Waal, A.M.* ; Kraft, D. ; Hiemstra, P.S.* ; Ryan, A.L.* ; van der Does, A.M.*

Breathing on chip: Dynamic flow and stretch accelerate mucociliary maturation of airway epithelium in vitro

Mater. Today Bio 21:100713 (2023)
Publ. Version/Full Text DOI PMC
Creative Commons Lizenzvertrag
Human lung function is intricately linked to blood flow and breathing cycles, but it remains unknown how these dynamic cues shape human airway epithelial biology. Here we report a state-of-the-art protocol for studying the effects of dynamic medium and airflow as well as stretch on human primary airway epithelial cell differentiation and maturation, including mucociliary clearance, using an organ-on-chip device. Perfused epithelial cell cultures displayed accelerated maturation and polarization of mucociliary clearance, and changes in specific cell-types when compared to traditional (static) culture methods. Additional application of airflow and stretch to the airway chip resulted in an increase in polarization of mucociliary clearance towards the applied flow, reduced baseline secretion of interleukin-8 and other inflammatory proteins, and reduced gene expression of matrix metalloproteinase (MMP) 9, fibronectin, and other extracellular matrix factors. These results indicate that breathing-like mechanical stimuli are important modulators of airway epithelial cell differentiation and maturation and that their fine-tuned application could generate models of specific epithelial pathologies, including mucociliary (dys)function.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Airflow ; Airway Epithelium ; Mechanobiology ; Mucociliary Clearance ; Organs-on-chips; Basal-cells; Platform; Culture; Cilia
ISSN (print) / ISBN 2590-0064
e-ISSN 2590-0064
Journal Materials Today Bio
Quellenangaben Volume: 21, Issue: , Pages: , Article Number: 100713 Supplement: ,
Publisher Elsevier
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Institute of Biological and Medical Imaging (IBMI)
Grants Marie Curie Actions (MSCA)

ERC-STG (MecCOPD)
Cystic Fibrosis Foundation
Tyler Health and Education Trust
Hastings Foundation
Lung Foundation Netherlands
Netherlands Organization for Health Research and Development (ZonMw)
Dutch Society for the Replacement of Animal Testing (Stichting Proefdiervrij)
EU Marie Curie Global Fellowship