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Idiopathic pulmonary fibrosis-on-chip: A new model based on biological membranes

P Zamprogno, J Schulte, T Weber, A Sengupta, T Geiser, O T Guenat
European Respiratory Journal 2022 60: 4634; DOI: 10.1183/13993003.congress-2022.4634
P Zamprogno
1Organs-on-Chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland
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J Schulte
1Organs-on-Chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland
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T Weber
1Organs-on-Chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland
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A Sengupta
1Organs-on-Chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland
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T Geiser
2Department of Pulmonary Medicine, University Hospital of Bern, Bern, Switzerland
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O T Guenat
1Organs-on-Chip Technologies Laboratory, ARTORG Center, University of Bern, Bern, Switzerland
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and severe lung disease characterized by a progressive scarring of the gas exchange airways. Despite two approved drugs that slow the disease progression, there is no effective therapy. Advanced in vitro models, called lung-on-chip, are emerging as a promising tool for lung disease research. Here, we report the development of an IPF-on-chip model designed to reproduce the biophysical cellular environment of the early and the late stage of lung fibrosis.

The model is based on biological membranes supported by a hexagonal gold mesh that forms an array of alveoli with in vivo-like dimensions. The mechanical properties of the membranes are largely influenced by the fabrication process. Their stiffness ranges from 1kPa to 170kPa, allowing the reproduction of the healthy and fibrotic tissue.

The biological membranes provide good support for cell growth and proliferation. We found that human primary fibroblasts treated with TGF-β secreted more collagen and fibronectin than untreated cells in three patients. In addition, human primary alveolar cells were successfully isolated and grown in organoids in Matrigel, allowing their dissociation and used as needed. After five days in culture in our model, a large percentage of alveolar epithelial cells expressed HTII-280 marker, a typical protein of type II alveolar cells, and formed a tight barrier. Further studies on the effect of antifibrotic drugs will be conducted.

In summary, this model reproduces some key features of the lung fibrosis alveolar environment in terms of structure, extracellular matrix composition and mechanical properties. Its entire biological nature makes it a promising tool for drug discovery.

  • Idiopathic pulmonary fibrosis
  • Experimental approaches
  • Epithelial cell

Footnotes

Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4634.

This article was presented at the 2022 ERS International Congress, in session “-”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2022
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Idiopathic pulmonary fibrosis-on-chip: A new model based on biological membranes
P Zamprogno, J Schulte, T Weber, A Sengupta, T Geiser, O T Guenat
European Respiratory Journal Sep 2022, 60 (suppl 66) 4634; DOI: 10.1183/13993003.congress-2022.4634

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Idiopathic pulmonary fibrosis-on-chip: A new model based on biological membranes
P Zamprogno, J Schulte, T Weber, A Sengupta, T Geiser, O T Guenat
European Respiratory Journal Sep 2022, 60 (suppl 66) 4634; DOI: 10.1183/13993003.congress-2022.4634
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