Long‐term expanding human airway organoids for disease modeling

• Norman Sachs ^[2] ; Angelos Papaspyropoulos ^[2] ; Domenique D Zomer‐van Ommen ^[3] ; Inha Heo ^[2] ; Lena Böttinger ^[2] ; Dymph Klay ^[4] ; Fleur Weeber ^[5] ; Guizela Huelsz‐Prince ^[6] ; Nino Iakobachvili ^[1] ; Gimano D Amatngalim ^[3] ; Joep de Ligt ^[7] ; Arne van Hoeck ^[7] ; Natalie Proost ^[8] ; Marco C Viveen ^[7] ; Anna Lyubimova ^[2] ; Luc Teeven ^[2] ; Sepideh Derakhshan ^[3] ; Jeroen Korving ^[2] ; Harry Begthel ^[2] ; Johanna F Dekkers ^[2] ; Kuldeep Kumawat ^[3] ; Emilio Ramos ^[9] ; Matthijs FM van Oosterhout ^[4] ; G Johan Offerhaus ^[7] ; Dominique J Wiener ^[2] ; Eduardo P Olimpio ^[6] ; Krijn K Dijkstra ^[5] ; Egbert F Smit ^[5] ; Maarten van der Linden ^[3] ; Sridevi Jaksani ^[9] ; Marieke van de Ven ^[8] ; Jos Jonkers ^[8] ; Anne C Rios ^[10] ; Emile E Voest ^[5] ; Coline HM van Moorsel ^[4] ; Cornelis K van der Ent ^[3] ; Edwin Cuppen ^[7] ; Alexander van Oudenaarden ^[2] ; Frank E Coenjaerts ^[7] ; Linde Meyaard ^[3] ; Louis J Bont ^[3] ; Peter J Peters ^[1] ; Sander J Tans ^[6] ; Jeroen S van Zon ^[6] ; Sylvia F Boj ^[9] ; Robert G Vries ^[9] ; Jeffrey M Beekman ^[3] ; Hans Clevers ^[11]
  1. [1] Maastricht University

     Maastricht University

     Países Bajos

     
  2. [2] 1 Oncode Institute Hubrecht Institute‐KNAW and UMC Utrecht Utrecht The Netherlands
  3. [3] 2 Wilhelmina Children's Hospital and UMC Utrecht Utrecht The Netherlands
  4. [4] 3 St. Antonius Hospital Nieuwegein Nieuwegein The Netherlands
  5. [5] 4 The Netherlands Cancer Institute Amsterdam The Netherlands
  6. [6] 5 FOM Institute AMOLF Amsterdam The Netherlands
  7. [7] 7 UMC Utrecht Utrecht The Netherlands
  8. [8] 8 Mouse Clinic for Cancer and Aging (MCCA) Preclinical Intervention Unit The Netherlands Cancer Institute Amsterdam The Netherlands
  9. [9] 9 Hubrecht Organoid Technology Utrecht The Netherlands
  10. [10] 10 Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
  11. [11] 1 Oncode Institute Hubrecht Institute‐KNAW and UMC Utrecht Utrecht The Netherlands; 10 Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

  Mostrar afiliaciones +
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 4, 2019
• Idioma: inglés
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• Resumen

  • 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.