@article{1501, keywords = {3D culture, Animals, Carcinoma, Non-Small-Cell Lung, Cells, Cultured, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Disease Models, Animal, Drug Screening Assays, Antitumor, Epithelial Cells, Female, Humans, Lung Neoplasms, Male, Mice, Mice, Inbred NOD, Mice, SCID, Organ Culture Techniques, organoids, Respiratory Syncytial Virus Infections, Respiratory Syncytial Viruses, Respiratory System, Xenograft Model Antitumor Assays, airway organoids, Cystic Fibrosis, lung cancer, respiratory syncytial virus}, author = {Norman Sachs and Angelos Papaspyropoulos and Domenique D. Zomer-van Ommen and Inha Heo and Lena Böttinger and Dymph Klay and Fleur Weeber and Guizela Huelsz-Prince and Nino Iakobachvili and Gimano D. Amatngalim and Joep de Ligt and Arne van Hoeck and Natalie Proost and Marco C. Viveen and Anna Lyubimova and Luc Teeven and Sepideh Derakhshan and Jeroen Korving and Harry Begthel and Johanna F. Dekkers and Kuldeep Kumawat and Emilio Ramos and Matthijs Fm van Oosterhout and G. Johan Offerhaus and Dominique J. Wiener and Eduardo P. Olimpio and Krijn K. Dijkstra and Egbert F. Smit and Maarten van der Linden and Sridevi Jaksani and Marieke van de Ven and Jos Jonkers and Anne C. Rios and Emile E. Voest and Coline Hm van Moorsel and Cornelis K. van der Ent and Edwin Cuppen and Alexander van Oudenaarden and Frank E. Coenjaerts and Linde Meyaard and Louis J. Bont and Peter J. Peters and Sander J. Tans and Jeroen S. van Zon and Sylvia F. Boj and Robert G. Vries and Jeffrey M. Beekman and Hans Clevers}, title = {Long-term expanding human airway organoids for disease modeling}, abstract = {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 resections or lavage material. The pseudostratified airway organoids consist of basal cells, functional multi-ciliated cells, mucus-producing secretory cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoids established from lung cancer resections and metastasis biopsies retain tumor histopathology as well as cancer gene mutations and are amenable to drug screening. Respiratory syncytial virus (RSV) infection recapitulates central disease features, dramatically increases organoid cell motility via the non-structural viral NS2 protein, and preferentially recruits neutrophils upon co-culturing. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.}, year = {2019}, journal = {The EMBO journal}, volume = {38}, pages = {e100300}, month = {2019-02-15}, issn = {1460-2075}, doi = {10.15252/embj.2018100300}, language = {eng}, }