A novel in vitro tubular model to recapitulate features of distal airways: the bronchioid
Abstract Background Airflow limitation is the hallmark of obstructive pulmonary diseases. While numerousin vitroairway models already exist, chronic obstructives diseases currently lack an 3D culture system enabling to unveil the developmental processes underlying airway remodelling and the associated constrictive limitation. Here, we aimed to engineer a model of small airways, which would overcome the limitations of current culture systems.Methods Working with the Cellular Capsule Technology, we developed a so-called bronchioid model, using an innovative tubular cell-based assay and human bronchial adult stem cells derived from clinical samples.Results We produced a tubular scaffold made of alginate gel, that drives the spontaneous self-organisation of epithelial cells. Fine control of the level of contraction is required to obtain a model of distal bronchiole, with physiologically relevant shape and size. 3D imaging, gene expression and single-cell RNA-seq analysis of bronchioids made of bronchial epithelial cells demonstrates the tubular organization, the formation of epithelial junctions, as well as differentiation into ciliated and goblet cells. Ciliary beating is observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid can be infected by rhinovirus. An air-liquid interface is introduced, that modulates gene expression.Conclusion We provide here a proof of concept of a perfusable bronchioid, with proper mucociliary and contractile functions. Key advantages of our approach, such as the air-liquid interface, the lumen accessibility, the recapitulation of pathological features and possible assessment of clinically pertinent endpoints, will make our pulmonary organoid-like model a powerful tool for pre-clinical studies..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 22. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Maurat, Elise [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.12.06.569771 |
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| PPN (Katalog-ID): |
XBI041801776 |
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| 520 | |a Abstract Background Airflow limitation is the hallmark of obstructive pulmonary diseases. While numerousin vitroairway models already exist, chronic obstructives diseases currently lack an 3D culture system enabling to unveil the developmental processes underlying airway remodelling and the associated constrictive limitation. Here, we aimed to engineer a model of small airways, which would overcome the limitations of current culture systems.Methods Working with the Cellular Capsule Technology, we developed a so-called bronchioid model, using an innovative tubular cell-based assay and human bronchial adult stem cells derived from clinical samples.Results We produced a tubular scaffold made of alginate gel, that drives the spontaneous self-organisation of epithelial cells. Fine control of the level of contraction is required to obtain a model of distal bronchiole, with physiologically relevant shape and size. 3D imaging, gene expression and single-cell RNA-seq analysis of bronchioids made of bronchial epithelial cells demonstrates the tubular organization, the formation of epithelial junctions, as well as differentiation into ciliated and goblet cells. Ciliary beating is observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid can be infected by rhinovirus. An air-liquid interface is introduced, that modulates gene expression.Conclusion We provide here a proof of concept of a perfusable bronchioid, with proper mucociliary and contractile functions. Key advantages of our approach, such as the air-liquid interface, the lumen accessibility, the recapitulation of pathological features and possible assessment of clinically pertinent endpoints, will make our pulmonary organoid-like model a powerful tool for pre-clinical studies. | ||
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| 700 | 1 | |a Leipold, Alexander M. |4 aut | |
| 700 | 1 | |a Henrot, Pauline |4 aut | |
| 700 | 1 | |a Zysman, Maeva |4 aut | |
| 700 | 1 | |a Prevel, Renaud |4 aut | |
| 700 | 1 | |a Trian, Thomas |4 aut | |
| 700 | 1 | |a Krammer, Tobias |4 aut | |
| 700 | 1 | |a Bergeron, Vanessa |4 aut | |
| 700 | 1 | |a Thumerel, Matthieu |4 aut | |
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| 700 | 1 | |a Berger, Patrick |4 aut | |
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| 700 | 1 | |a Dupin, Isabelle |0 (orcid)0000-0002-4992-9625 |4 aut | |
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