A novel in vitro tubular model to recapitulate features of distal airways: The bronchioid.

Autor:	Maurat E; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; equal contribution (co1st author)., Raasch K; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; equal contribution (co1st author)., Leipold AM; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany., Henrot P; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, France., Zysman M; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, France., Prevel R; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, France., Trian T; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France., Krammer T; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany., Bergeron V; VoxCell Facility, TBMcore UAR CNRS 3427, INSERM US 005, Univ-Bordeaux, France., Thumerel M; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, France., Nassoy P; Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, France., Berger P; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; CHU de Bordeaux, Service d'exploration fonctionnelle respiratoire, Service de réanimation, Service de chirurgie thoracique, France., Saliba AE; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.; University of Würzburg, Faculty of Medicine, Institute of Molecular Infection Biology (IMIB), Würzburg, Germany., Andrique L; VoxCell Facility, TBMcore UAR CNRS 3427, INSERM US 005, Univ-Bordeaux, France., Recher G; Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, France., Dupin I; Univ-Bordeaux, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France isabelle.dupin@u-bordeaux.fr.; INSERM, Centre de Recherche Cardio-thoracique de Bordeaux, U1045, CIC1401, Pessac, France.; Institut Universitaire de France (IUF).
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2024 Sep 04. Date of Electronic Publication: 2024 Sep 04.
DOI:	10.1183/13993003.00562-2024
Abstrakt:	Background: Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous in vitro models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems. Methods: We developed a so-called bronchioid model by encapsulating human bronchial adult stem cells derived from clinical samples in a tubular scaffold made of alginate gel. Results: This template drives the spontaneous self-organisation of epithelial cells into a tubular structure. Fine control of the level of contraction is required to establish a model of the bronchiole, which has a physiologically relevant shape and size. 3D imaging, gene expression and single-cell RNA-seq analysis of bronchioids made of bronchial epithelial cells revealed tubular organisation, epithelial junction formation and 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: Here, we provide a proof of concept of a perfusable bronchioid with proper mucociliary and contractile functions. The key advantages of our approach, such as the air‒liquid interface, lumen accessibility, recapitulation of pathological features and possible assessment of clinically relevant endpoints, will make our pulmonary organoid-like model a powerful tool for preclinical studies. (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)
Databáze:	MEDLINE
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