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A novel in vitro tubular model to recapitulate features of distal airways: The bronchioid
HENROT, Pauline
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
ZYSMAN, Maeva
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
PREVEL, Renaud
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
THUMEREL, Matthieu
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
BERGER, Patrick
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
SALIBA, Antoine-Emmanuel
Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany] [JMU]
Helmholtz Centre for Infection Research [HZI]
Julius-Maximilians-Universität Würzburg = University of Würzburg [Würsburg, Germany] [JMU]
Helmholtz Centre for Infection Research [HZI]
DUPIN, Isabelle
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Institut universitaire de France [IUF]
< Reduce
Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB]
CIC Bordeaux
Institut universitaire de France [IUF]
Language
EN
Article de revue
This item was published in
European Respiratory Journal. 2024-09-04p. Online ahead of print
English Abstract
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 ...Read more >
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.Read less <