Long-term expanding human airway organoids for disease modeling

Norman Sachs, Angelos Papaspyropoulos, Domenique D. Zomer-van Ommen, Inha Heo, Lena Bottinger, Dymph Klay, Fleur Weeber, Guizela Huelsz-Prince, Nino Iakobachvili, Gimano D. Amatngalim, Joep de Ligt, Arne van Hoeck, Natalie Proost, Marco C. Viveen, Anna Lyubimova, Luc Teeven, Sepideh Derakhshan, Jeroen Korving, Harry Begthel, Johanna F. DekkersKuldeep Kumawat, Emilio Ramos, Matthijs F. M. van Oosterhout, G. Johan Offerhaus, Dominique J. Wiener, Eduardo P. Olimpio, Krijn K. Dijkstra, Egbert F. Smit, Maarten van der Linden, Sridevi Jaksani, Marieke van de Ven, Jos Jonkers, Anne C. Rios, Emile E. Voest, Coline H. M. van Moorsel, Cornelis K. van der Ent, Edwin Cuppen, Alexander van Oudenaarden, Frank E. Coenjaerts, Linde Meyaard, Louis J. Bont, Peter J. Peters, Sander J. Tans, Jeroen S. van Zon, Sylvia F. Boj, Robert G. Vries, Jeffrey M. Beekman, Hans Clevers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

331 Citations (Web of Science)

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.

Original languageEnglish
Article number100300
Number of pages20
JournalThe Embo Journal
Volume38
Issue number4
DOIs
Publication statusPublished - 15 Feb 2019

Keywords

  • 3D culture
  • airway organoids
  • cystic fibrosis
  • lung cancer
  • respiratory syncytial virus
  • PLURIPOTENT STEM-CELLS
  • CYSTIC-FIBROSIS
  • CHLORIDE CHANNEL
  • BASAL-CELLS
  • EPITHELIUM
  • REGENERATION
  • TARGET
  • GENERATION
  • DERIVATION
  • INHIBITION

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