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 language | English |
---|---|
Article number | 100300 |
Number of pages | 20 |
Journal | The Embo Journal |
Volume | 38 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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
Access to Document
- 10.15252/embj.2018100300Licence: CC BY-NC-ND
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In: The Embo Journal, Vol. 38, No. 4, 100300, 15.02.2019.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Long-term expanding human airway organoids for disease modeling
AU - Sachs, Norman
AU - Papaspyropoulos, Angelos
AU - Zomer-van Ommen, Domenique D.
AU - Heo, Inha
AU - Bottinger, Lena
AU - Klay, Dymph
AU - Weeber, Fleur
AU - Huelsz-Prince, Guizela
AU - Iakobachvili, Nino
AU - Amatngalim, Gimano D.
AU - de Ligt, Joep
AU - van Hoeck, Arne
AU - Proost, Natalie
AU - Viveen, Marco C.
AU - Lyubimova, Anna
AU - Teeven, Luc
AU - Derakhshan, Sepideh
AU - Korving, Jeroen
AU - Begthel, Harry
AU - Dekkers, Johanna F.
AU - Kumawat, Kuldeep
AU - Ramos, Emilio
AU - van Oosterhout, Matthijs F. M.
AU - Offerhaus, G. Johan
AU - Wiener, Dominique J.
AU - Olimpio, Eduardo P.
AU - Dijkstra, Krijn K.
AU - Smit, Egbert F.
AU - van der Linden, Maarten
AU - Jaksani, Sridevi
AU - van de Ven, Marieke
AU - Jonkers, Jos
AU - Rios, Anne C.
AU - Voest, Emile E.
AU - van Moorsel, Coline H. M.
AU - van der Ent, Cornelis K.
AU - Cuppen, Edwin
AU - van Oudenaarden, Alexander
AU - Coenjaerts, Frank E.
AU - Meyaard, Linde
AU - Bont, Louis J.
AU - Peters, Peter J.
AU - Tans, Sander J.
AU - van Zon, Jeroen S.
AU - Boj, Sylvia F.
AU - Vries, Robert G.
AU - Beekman, Jeffrey M.
AU - Clevers, Hans
N1 - Funding Information: We would like to acknowledge Carmen Lopez-Iglesias for supporting high-pressure freezing and freeze substitution. We thank Raimond Ravelli for providing transmission EM overview software and Antoni P.A. Hendrickx for help with scanning EM. We acknowledge Anko de Graaff and the Hubrecht Imaging Center for supporting light microscopy. We thank Inez Bronsveld for obtaining intestinal biopsies. We thank people from the Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI for performing the intervention studies. We acknowledge UBEC and USEQ. We thank the WKZ Pediatric Pulmonology Department for obtaining lavage fluid. We are grateful to Stieneke van den Brink and Nilofar Ehsani for preparing media. Genetically modified RSV variants were generously provided by Peter Collins, Mark E. Peeples, and Ulla Buchholz. We thank the Multiplex Core facility of the LTI UMC Utrecht for developing, validating, and performing immunoassays. Work at the Hubrecht Institute was supported by MKMD and VENI grants from the Dutch Organization of Scientific Research NWO (ZonMw 114021012 and 916.15.182), a Stand Up to Cancer International Translational Cancer Research Grant (a program of the Entertainment Industry Foundation administered by the AACR) and an Alpe d'Huze/KWF program grant (2014-7006). This work is part of the Oncode Institute which is partly financed by the Dutch Cancer Society and was funded by the gravitation program CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research (NWO). The spinning disk microscope is funded by NWO equipment grant 834.11.002. Work in the laboratory of S.J.T. is part of the research program of the Foundation for Fundamental Research on Matter (FOM), as part of NWO. The work of G.H. and J.S.Z. was supported by a NWO VIDI grant (680-47-529) and a HFSP Career Development Award (CDA00076/2014-C). Work at the St. Antonius Hospital was supported by the Prof. Dr. Jaap Swierenga Foundation (development of human lung organoids). J.M.B., D.Z., and C.K.E. were supported by a grant from The Netherlands Organisation for Health Research and Development (ZonMW 40-00812-98-14103) and the Dutch Cystic Fibrosis Society (HIT-CF program). Funding Information: We would like to acknowledge Carmen Lopez-Iglesias for supporting high-pressure freezing and freeze substitution. We thank Raimond Ravelli for providing transmission EM overview software and Antoni P.A. Hendrickx for help with scanning EM. We acknowledge Anko de Graaff and the Hubrecht Imaging Center for supporting light microscopy. We thank Inez Bronsveld for obtaining intestinal biopsies. We thank people from the Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI for performing the intervention studies. We acknowledge UBEC and USEQ. We thank the WKZ Pediatric Pulmonology Department for obtaining lavage fluid. We are grateful to Stieneke van den Brink and Nilofar Ehsani for preparing media. Genetically modified RSV variants were generously provided by Peter Collins, Mark E. Peeples, and Ulla Buch-holz. We thank the Multiplex Core facility of the LTI UMC Utrecht for developing, validating, and performing immunoassays. Work at the Hubrecht Institute was supported by MKMD and VENI grants from the Dutch Organization of Scientific Research NWO (ZonMw 114021012 and 916.15.182), a Stand Up to Cancer International Translational Cancer Research Grant (a program of the Entertainment Industry Foundation administered by the AACR) and an Alpe d’Huze/KWF program grant (2014-7006). This work is part of the Oncode Institute which is partly financed by the Dutch Cancer Society and was funded by the gravitation program CancerGenomiCs.nl from the Netherlands Organisation for Scientific Research (NWO). The spinning disk microscope is funded by NWO equipment grant 834.11.002. Work in the laboratory of S.J.T. is part of the research program of the Foundation for Fundamental Research on Matter (FOM), as part of NWO. The work of G.H. and J.S.Z. was supported by a NWO VIDI grant (680-47-529) and a HFSP Career Development Award (CDA00076/2014-C). Work at the St. Antonius Hospital was supported by the Prof. Dr. Jaap Swierenga Foundation (development of human lung organoids). J.M.B., D.Z., and C.K.E. were supported by a grant from The Netherlands Organisation for Health Research and Development (ZonMW 40-00812-98-14103) and the Dutch Cystic Fibrosis Society (HIT-CF program). Publisher Copyright: © 2019 The Authors. Published under the terms of the CC BY NC ND 4.0 license
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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.
AB - 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.
KW - 3D culture
KW - airway organoids
KW - cystic fibrosis
KW - lung cancer
KW - respiratory syncytial virus
KW - PLURIPOTENT STEM-CELLS
KW - CYSTIC-FIBROSIS
KW - CHLORIDE CHANNEL
KW - BASAL-CELLS
KW - EPITHELIUM
KW - REGENERATION
KW - TARGET
KW - GENERATION
KW - DERIVATION
KW - INHIBITION
U2 - 10.15252/embj.2018100300
DO - 10.15252/embj.2018100300
M3 - Article
C2 - 30643021
SN - 0261-4189
VL - 38
JO - The Embo Journal
JF - The Embo Journal
IS - 4
M1 - 100300
ER -