TY - JOUR
KW - 3D culture
KW - Animals
KW - Carcinoma, Non-Small-Cell Lung
KW - Cells, Cultured
KW - Cystic Fibrosis
KW - Cystic Fibrosis Transmembrane Conductance Regulator
KW - Disease Models, Animal
KW - Drug Screening Assays, Antitumor
KW - Epithelial Cells
KW - Female
KW - Humans
KW - Lung Neoplasms
KW - Male
KW - Mice
KW - Mice, Inbred NOD
KW - Mice, SCID
KW - Organ Culture Techniques
KW - organoids
KW - Respiratory Syncytial Virus Infections
KW - Respiratory Syncytial Viruses
KW - Respiratory System
KW - Xenograft Model Antitumor Assays
KW - airway organoids
KW - Cystic Fibrosis
KW - lung cancer
KW - respiratory syncytial virus
AU - Norman Sachs
AU - Angelos Papaspyropoulos
AU - Domenique D. Zomer-van Ommen
AU - Inha Heo
AU - Lena Böttinger
AU - Dymph Klay
AU - Fleur Weeber
AU - Guizela Huelsz-Prince
AU - Nino Iakobachvili
AU - Gimano D. Amatngalim
AU - Joep de Ligt
AU - Arne van Hoeck
AU - Natalie Proost
AU - Marco C. Viveen
AU - Anna Lyubimova
AU - Luc Teeven
AU - Sepideh Derakhshan
AU - Jeroen Korving
AU - Harry Begthel
AU - Johanna F. Dekkers
AU - Kuldeep Kumawat
AU - Emilio Ramos
AU - Matthijs Fm van Oosterhout
AU - G. Johan Offerhaus
AU - Dominique J. Wiener
AU - Eduardo P. Olimpio
AU - Krijn K. Dijkstra
AU - Egbert F. Smit
AU - Maarten van der Linden
AU - Sridevi Jaksani
AU - Marieke van de Ven
AU - Jos Jonkers
AU - Anne C. Rios
AU - Emile E. Voest
AU - Coline Hm 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
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 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.
BT - The EMBO journal
DA - 2019-02-15
DO - 10.15252/embj.2018100300
IS - 4
LA - eng
N2 - 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.
PY - 2019
EP - e100300
T2 - The EMBO journal
TI - Long-term expanding human airway organoids for disease modeling
VL - 38
SN - 1460-2075
ER -