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 as joint first authors., 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 as joint first authors., Leipold AM; 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., 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, Bordeaux, 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, Bordeaux, 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, Bordeaux, 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, 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, Bordeaux, France., Nassoy P; Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, 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, Bordeaux, 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, Bordeaux, France., Recher G; Laboratoire Photonique, Numérique et Nanosciences, UMR 5298 CNRS, Univ-Bordeaux, 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), Paris, France.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2024 Dec 05; Vol. 64 (6). Date of Electronic Publication: 2024 Dec 05 (Print Publication: 2024).
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. Three-dimensional imaging, gene expression and single-cell RNA-sequencing analysis of bronchioids made of bronchial epithelial cells revealed tubular organisation, epithelial junction formation and differentiation into ciliated and goblet cells. Ciliary beating was observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid could be infected by rhinovirus. An air-liquid interface was introduced that modulated 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 end-points, will make our pulmonary organoid-like model a powerful tool for preclinical studies. Competing Interests: Conflict of interest: I. Dupin and P. Berger have two patents (EP number 3050574 and EP number 20173595). I. Dupin, P. Henrot and M. Zysman report grants from the Fondation Bordeaux Université. M. Zysman reports personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Novartis, Chiesi and GlaxoSmithKline, and non-financial support from Lilly. P. Berger reports grants and personal fees from Novartis; personal fees and non-financial support from Chiesi, Boehringer Ingelheim, AstraZeneca and Sanofi; and personal fees from Menarini and TEVA, outside the submitted work. All other authors declare that they have no competing interests. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
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