医学
纤毛
小型航空公司
细支气管
体外
细胞生物学
病理
解剖
免疫学
呼吸系统
生物
哮喘
生物化学
作者
Élise Maurat,Katharina Raasch,Alexander Leipold,Pauline Henrot,M. Zysman,Renaud Prével,Thomas Trian,Tobias Krammer,Vanessa Bergeron,Matthieu Thumerel,Pierre Nassoy,Patrick Berger,Antoine‐Emmanuel Saliba,Laëtitia Andrique,Gaëlle Recher,Isabelle Dupin
出处
期刊:The European respiratory journal
[European Respiratory Society]
日期:2024-09-04
卷期号:: 2400562-2400562
标识
DOI:10.1183/13993003.00562-2024
摘要
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.
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