03909nas a2201021   4500000000100000000000100001008004100002260001500043653001500058653001200073653003500085653002000120653002000140653005600160653002700216653003700243653002100280653001100301653001100312653001900323653000900342653000900351653002100360653001500381653002900396653001400425653004300439653003400482653002300516653003700539653002100576653002000597653001600617653003200633100001700665700002800682700003300710700001300743700002000756700001500776700001700791700002600808700002200834700002500856700001700881700001900898700001900917700002000936700001900956700001500975700002300990700001901013700001801032700002301050700002001073700001701093700003101110700002301141700002401164700002301188700002201211700001901233700002701252700002001279700002301299700001601322700001701338700001901355700002601374700002801400700001701428700003001445700002401475700001801499700001801517700002001535700001901555700002201574700001801596700002001614700002301634700001701657245006801674300001201742490000701754520111201761022001402873       2019                            d  c2019-02-1510a3D culture10aAnimals10aCarcinoma, Non-Small-Cell Lung10aCells, Cultured10aCystic Fibrosis10aCystic Fibrosis Transmembrane Conductance Regulator10aDisease Models, Animal10aDrug Screening Assays, Antitumor10aEpithelial Cells10aFemale10aHumans10aLung Neoplasms10aMale10aMice10aMice, Inbred NOD10aMice, SCID10aOrgan Culture Techniques10aorganoids10aRespiratory Syncytial Virus Infections10aRespiratory Syncytial Viruses10aRespiratory System10aXenograft Model Antitumor Assays10aairway organoids10aCystic Fibrosis10alung cancer10arespiratory syncytial virus1 aNorman Sachs1 aAngelos Papaspyropoulos1 aDomenique D. Zomer-van Ommen1 aInha Heo1 aLena Böttinger1 aDymph Klay1 aFleur Weeber1 aGuizela Huelsz-Prince1 aNino Iakobachvili1 aGimano D. Amatngalim1 aJoep de Ligt1 aArne van Hoeck1 aNatalie Proost1 aMarco C. Viveen1 aAnna Lyubimova1 aLuc Teeven1 aSepideh Derakhshan1 aJeroen Korving1 aHarry Begthel1 aJohanna F. Dekkers1 aKuldeep Kumawat1 aEmilio Ramos1 aMatthijs Fm van Oosterhout1 aG. Johan Offerhaus1 aDominique J. Wiener1 aEduardo P. Olimpio1 aKrijn K. Dijkstra1 aEgbert F. Smit1 aMaarten van der Linden1 aSridevi Jaksani1 aMarieke van de Ven1 aJos Jonkers1 aAnne C. Rios1 aEmile E. Voest1 aColine Hm van Moorsel1 aCornelis K. van der Ent1 aEdwin Cuppen1 aAlexander van Oudenaarden1 aFrank E. Coenjaerts1 aLinde Meyaard1 aLouis J. Bont1 aPeter J. Peters1 aSander J. Tans1 aJeroen S. van Zon1 aSylvia F. Boj1 aRobert G. Vries1 aJeffrey M. Beekman1 aHans Clevers00aLong-term expanding human airway organoids for disease modeling  ae1003000 v383 aOrganoids 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.  a1460-2075