Long‐term expanding human airway organoids for disease modeling

By Norman Sachs, A. Papaspyropoulos, D. Z. Zomer-van Ommen, Inha Heo, L. Böttinger, Dymph Klay, F. Weeber, Guizela Huelsz-Prince, Nino Iakobachvili, G. Amatngalim and 38 more. EMBO Journal, 2019

939 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/21f6be482fbf6a8931c45829ccada41b00f8b585

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In Molecular Biology

1. Hans Clevers
2. E. Voest
3. R. Nusse
4. Elaine Fuchs
5. C. Blanpain
6. M. Resh
7. Jessica Rios-Esteves
8. Pengfei Lu

In Pulmonary and Respiratory Medicine

1. Hans Clevers

Citations in the corpus

• Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids (2018, positive): “To select for tumor organoids, we applied the MDM-2 inhibitor Nutlin-3a to selectively grow out p53 mutant cells of this sample, resulting in a pure tumor organoid population (Sachs et al., 2018).”
• Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening (2019, neutral): “(%) Adenocarcinoma 20 (51) 12 (31) Squamous cell carcinoma 9 (23) 3 (8) Large cell carcinoma 2 (5) 1 (3) Small cell carcinoma 5 (13) 0 (0) Adenosquamous carcinoma 1 (3) 1 (3) Normal bronchial organoid 2 (5) 0 (0) Total (56 samples) 39 (70) 17 (30) NATURE COMMUNICATIONS | https://doi.”