Long‐term expanding human airway organoids for disease modeling

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 o...

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Published in:	The EMBO journal Vol. 38; no. 4
Main Authors:	Sachs, Norman, Papaspyropoulos, Angelos, Zomer‐van Ommen, Domenique D, Heo, Inha, Böttinger, Lena, Klay, Dymph, Weeber, Fleur, Huelsz‐Prince, Guizela, Iakobachvili, Nino, Amatngalim, Gimano D, de Ligt, Joep, van Hoeck, Arne, Proost, Natalie, Viveen, Marco C, Lyubimova, Anna, Teeven, Luc, Derakhshan, Sepideh, Korving, Jeroen, Begthel, Harry, Dekkers, Johanna F, Kumawat, Kuldeep, Ramos, Emilio, van Oosterhout, Matthijs FM, Offerhaus, G Johan, Wiener, Dominique J, Olimpio, Eduardo P, Dijkstra, Krijn K, Smit, Egbert F, van der Linden, Maarten, Jaksani, Sridevi, van de Ven, Marieke, Jonkers, Jos, Rios, Anne C, Voest, Emile E, van Moorsel, Coline HM, van der Ent, Cornelis K, Cuppen, Edwin, van Oudenaarden, Alexander, Coenjaerts, Frank E, Meyaard, Linde, Bont, Louis J, Peters, Peter J, Tans, Sander J, van Zon, Jeroen S, Boj, Sylvia F, Vries, Robert G, Beekman, Jeffrey M, Clevers, Hans
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 15.02.2019 Springer Nature B.V John Wiley and Sons Inc
Subjects:	3D culture airway organoids Alveoli Animals Basal cells Cancer Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Cell culture Cells, Cultured Cystic fibrosis Cystic Fibrosis - metabolism Cystic Fibrosis - pathology Cystic Fibrosis Transmembrane Conductance Regulator - metabolism Disease Disease Models, Animal Drug screening Drug Screening Assays, Antitumor EMBO03 EMBO22 EMBO24 Epithelial Cells - metabolism Epithelial Cells - pathology Epithelium Female Hereditary diseases Histopathology Humans Leukocytes (neutrophilic) Lung cancer Lung diseases Lung Neoplasms - drug therapy Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Metastases Mice Mice, Inbred NOD Mice, SCID Mucous membrane Mucus Mutation NS2 protein Organ Culture Techniques - methods Organoids Organoids - metabolism Organoids - pathology Proteins Resource Respiratory syncytial virus Respiratory Syncytial Virus Infections - pathology Respiratory Syncytial Virus Infections - virology Respiratory Syncytial Viruses - isolation & purification Respiratory System - metabolism Respiratory System - pathology Respiratory tract Respiratory tract diseases Screening Stem cells Structure-function relationships Three dimensional models Viral infections Viruses Xenograft Model Antitumor Assays lung cancer 3D culture respiratory syncytial virus cystic fibrosis airway organoids
ISSN:	0261-4189, 1460-2075, 1460-2075
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Summary:	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. Synopsis To date, persistent in vitro culture of adult human lung epithelium remains elusive. In this methods resource article, culture conditions to maintain three‐dimensional pulmonary tissue long‐term are reported and applied to recapitulate related diseases. Culture conditions for long‐term expansion of healthy, hereditary disease and malignant human airway epithelial organoids. Airway organoids are amenable for medium‐throughput drug screening. Airway organoids readily allow modeling of viral infection. Graphical Abstract Three‐dimensional human pulmonary tissue culture allows for investigation of hereditary diseases.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 See also: M Paschini & CF Kim (February 2019)
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.15252/embj.2018100300