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Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip
The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360510/ https://www.ncbi.nlm.nih.gov/pubmed/30746362 http://dx.doi.org/10.3389/fbioe.2019.00003 |
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author | Felder, Marcel Trueeb, Bettina Stucki, Andreas Oliver Borcard, Sarah Stucki, Janick Daniel Schnyder, Bruno Geiser, Thomas Guenat, Olivier Thierry |
author_facet | Felder, Marcel Trueeb, Bettina Stucki, Andreas Oliver Borcard, Sarah Stucki, Janick Daniel Schnyder, Bruno Geiser, Thomas Guenat, Olivier Thierry |
author_sort | Felder, Marcel |
collection | PubMed |
description | The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a high degree of mechanical stress (>20% linear strain) is thought to potentially induce IPF, the effect of lower, physiological levels of strain (5–12% linear strain) on IPF pathophysiology remains unknown. In this study, we examined the influence of mechanical strain on alveolar epithelial wound healing. For this purpose, we adopted the “organ-on-a-chip” approach, which provides the possibility of reproducing unique aspects of the in vivo cellular microenvironment, in particular its dynamic nature. Our results provide the first demonstration that a wound healing assay can be performed on a breathing lung-on-a-chip equipped with an ultra-thin elastic membrane. We cultured lung alveolar epithelial cells to confluence, the cells were starved for 24 h, and then wounded by scratching with a standard micropipette tip. Wound healing was assessed after 24 h under different concentrations of recombinant human hepatic growth factor (rhHGF) and the application of cyclic mechanical stretch. Physiological cyclic mechanical stretch (10% linear strain, 0.2 Hz) significantly impaired the alveolar epithelial wound healing process relative to culture in static conditions. This impairment could be partially ameliorated by administration of rhHGF. This proof-of-concept study provides a way to study of more complex interactions, such as a co-culture with fibroblasts, endothelial cells, or immune cells, as well as the study of wound healing at an air–liquid interface. |
format | Online Article Text |
id | pubmed-6360510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63605102019-02-11 Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip Felder, Marcel Trueeb, Bettina Stucki, Andreas Oliver Borcard, Sarah Stucki, Janick Daniel Schnyder, Bruno Geiser, Thomas Guenat, Olivier Thierry Front Bioeng Biotechnol Bioengineering and Biotechnology The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a high degree of mechanical stress (>20% linear strain) is thought to potentially induce IPF, the effect of lower, physiological levels of strain (5–12% linear strain) on IPF pathophysiology remains unknown. In this study, we examined the influence of mechanical strain on alveolar epithelial wound healing. For this purpose, we adopted the “organ-on-a-chip” approach, which provides the possibility of reproducing unique aspects of the in vivo cellular microenvironment, in particular its dynamic nature. Our results provide the first demonstration that a wound healing assay can be performed on a breathing lung-on-a-chip equipped with an ultra-thin elastic membrane. We cultured lung alveolar epithelial cells to confluence, the cells were starved for 24 h, and then wounded by scratching with a standard micropipette tip. Wound healing was assessed after 24 h under different concentrations of recombinant human hepatic growth factor (rhHGF) and the application of cyclic mechanical stretch. Physiological cyclic mechanical stretch (10% linear strain, 0.2 Hz) significantly impaired the alveolar epithelial wound healing process relative to culture in static conditions. This impairment could be partially ameliorated by administration of rhHGF. This proof-of-concept study provides a way to study of more complex interactions, such as a co-culture with fibroblasts, endothelial cells, or immune cells, as well as the study of wound healing at an air–liquid interface. Frontiers Media S.A. 2019-01-22 /pmc/articles/PMC6360510/ /pubmed/30746362 http://dx.doi.org/10.3389/fbioe.2019.00003 Text en Copyright © 2019 Felder, Trueeb, Stucki, Borcard, Stucki, Schnyder, Geiser and Guenat. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Felder, Marcel Trueeb, Bettina Stucki, Andreas Oliver Borcard, Sarah Stucki, Janick Daniel Schnyder, Bruno Geiser, Thomas Guenat, Olivier Thierry Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title | Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title_full | Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title_fullStr | Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title_full_unstemmed | Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title_short | Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip |
title_sort | impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360510/ https://www.ncbi.nlm.nih.gov/pubmed/30746362 http://dx.doi.org/10.3389/fbioe.2019.00003 |
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