Chronic obstructive pulmonary disease (COPD) is a major public health disease characterized by chronic inflammation and remodelling. The lack of physiological relevance of traditional 2D cell culture models, as well as the limited predictibility of tests performed in animal models, strongly limit drug discovery.

In the present project, we aim to develop a 3D “bronchioid” model recapitulating the morphological and functional characteristics of distal airway, with a permissive and remodelable environment, using an innovative tubuloid cell-based assay and bronchial adult stem cell cells derived from clinical samples. Working with the unique cellular capsule technology [1Alessandri K., Sarangi B.R., Gurchenkov V.V., Sinha B., Kießling T.R., Fetler L., e al. Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro Proc Natl Acad Sci U S A 2013 ;  110 : 14843-14848 [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 2 Sci Adv 2019 ;  5 : 6562

Cliccare qui per andare alla sezione Riferimenti], we can produce a tubular scaffold made of alginate gel that will drive the spontaneous self-organisation of lung cells.

Our results show that fine tuning the balance between adhesion and contraction is required to obtain a model of bronchiole, with physiologically relevant shape and size. 3D imaging of organoids made of primary bronchial epithelial cells demonstrates the tubular organization and the existence of a lumen, as well as proper differentiation into ciliated and mucous cells. The bronchioid is perfusable, with medium or with air.

We provide here a proof of concept that we are able to build of a perfusable bronchioid, with proper mucociliary and contractile functions. Key advantages of our approach, such as the air–liquid interface, the lumen accessibility, and possible assessment of clinically pertinent endpoints, will make our pulmonary organoid a powerful tool for preclinical studies.