PT  - JOURNAL ARTICLE
AU  - Norman Sachs
AU  - Domenique D. Zomer-van Ommen
AU  - Angelos Papaspyropoulos
AU  - Inha Heo
AU  - Lena Böttinger
AU  - Dymph Klay
AU  - Fleur Weeber
AU  - Guizela Huelsz-Prince
AU  - Nino Iakobachvili
AU  - Marco C. Viveen
AU  - Anna Lyubimova
AU  - Luc Teeven
AU  - Sepideh Derakhshan
AU  - Jeroen Korving
AU  - Harry Begthel
AU  - Kuldeep Kumawat
AU  - Emilio Ramos
AU  - Matthijs F.M. van Oosterhout
AU  - Eduardo P. Olimpio
AU  - Joep de Ligt
AU  - Krijn K. Dijkstra
AU  - Egbert F. Smit
AU  - Maarten van der Linden
AU  - Emile E. Voest
AU  - Coline H.M. van Moorsel
AU  - Cornelis K. van der Ent
AU  - Edwin Cuppen
AU  - Alexander van Oudenaarden
AU  - Frank E. Coenjaerts
AU  - Linde Meyaard
AU  - Louis J. Bont
AU  - Peter J. Peters
AU  - Sander J. Tans
AU  - Jeroen S. van Zon
AU  - Sylvia F. Boj
AU  - Robert G. Vries
AU  - Jeffrey M. Beekman
AU  - Hans Clevers
TI  - Long-term expanding human airway organoids for disease modelling
AID  - 10.1101/318444
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 318444
4099  - http://biorxiv.org/content/early/2018/05/09/318444.short
4100  - http://biorxiv.org/content/early/2018/05/09/318444.full
AB  - Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.