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. Dekkers; Kuldeep 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

doi:10.15252/embj.2018100300

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 journal › Article › Academic › peer-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 language	English
Article number	100300
Number of pages	20
Journal	The Embo Journal
Volume	38
Issue number	4
DOIs	https://doi.org/10.15252/embj.2018100300
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.2018100300

Cite this

Sachs, N., Papaspyropoulos, A., Zomer-van Ommen, D. D., Heo, I., Bottinger, L., Klay, D., Weeber, F., Huelsz-Prince, G., Iakobachvili, N., Amatngalim, G. D., de Ligt, J., van Hoeck, A., Proost, N., Viveen, M. C., Lyubimova, A., Teeven, L., Derakhshan, S., Korving, J., Begthel, H., ... Clevers, H. (2019). Long-term expanding human airway organoids for disease modeling. The Embo Journal, 38(4), [100300]. https://doi.org/10.15252/embj.2018100300

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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, PLURIPOTENT STEM-CELLS, CYSTIC-FIBROSIS, CHLORIDE CHANNEL, BASAL-CELLS, EPITHELIUM, REGENERATION, TARGET, GENERATION, DERIVATION, INHIBITION",

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

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day = "15",

doi = "10.15252/embj.2018100300",

language = "English",

volume = "38",

journal = "The Embo Journal",

issn = "0261-4189",

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Sachs, N, Papaspyropoulos, A, Zomer-van Ommen, DD, Heo, I, Bottinger, L, Klay, D, Weeber, F, Huelsz-Prince, G, Iakobachvili, N, Amatngalim, GD, de Ligt, J, van Hoeck, A, Proost, N, Viveen, MC, Lyubimova, A, Teeven, L, Derakhshan, S, Korving, J, Begthel, H, Dekkers, JF, Kumawat, K, Ramos, E, van Oosterhout, MFM, Offerhaus, GJ, Wiener, DJ, Olimpio, EP, Dijkstra, KK, Smit, EF, van der Linden, M, Jaksani, S, van de Ven, M, Jonkers, J, Rios, AC, Voest, EE, van Moorsel, CHM, van der Ent, CK, Cuppen, E, van Oudenaarden, A, Coenjaerts, FE, Meyaard, L, Bont, LJ, Peters, PJ, Tans, SJ, van Zon, JS, Boj, SF, Vries, RG, Beekman, JM & Clevers, H 2019, 'Long-term expanding human airway organoids for disease modeling', The Embo Journal, vol. 38, no. 4, 100300. https://doi.org/10.15252/embj.2018100300

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

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

VL - 38

JO - The Embo Journal

JF - The Embo Journal

SN - 0261-4189

IS - 4

M1 - 100300

ER -