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EMBO J. 2019 Feb 15;38(4). pii: e100300. doi: 10.15252/embj.2018100300. Epub 2019 Jan 14.

Long-term expanding human airway organoids for disease modeling.

Author information

1
Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, Utrecht, The Netherlands.
2
Wilhelmina Children's Hospital and UMC Utrecht, Utrecht, The Netherlands.
3
St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.
4
The Netherlands Cancer Institute, Amsterdam, The Netherlands.
5
FOM Institute AMOLF, Amsterdam, The Netherlands.
6
Maastricht University, Maastricht, The Netherlands.
7
UMC Utrecht, Utrecht, The Netherlands.
8
Mouse Clinic for Cancer and Aging (MCCA) Preclinical Intervention Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
9
Hubrecht Organoid Technology, Utrecht, The Netherlands.
10
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
11
Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, Utrecht, The Netherlands h.clevers@hubrecht.eu.

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.

KEYWORDS:

3D culture; airway organoids; cystic fibrosis; lung cancer; respiratory syncytial virus

PMID:
30643021
DOI:
10.15252/embj.2018100300
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