Norman Sachs; Angelos Papaspyropoulos; Domenique D. Zomer-van Ommen; Inha Heo; Lena Böttinger; 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 FM van Oosterhout; G. Johan A. 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 HM van Moorsel; Cornelis K. van der Ent; Edwin Cuppen; Alexander van Oudenaarden; Frank E. J. Coenjaerts; Linde Meyaard; Louis Bont; Peter J. Peters; Sander J. Tans; Jeroen S. van Zon; Sylvia F. Boj; Robert G. Vries; Jeffrey M. Beekman; Hans Clevers · 2019 · The EMBO Journal
Paper
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. To date, persistent in vitro culture of adult human lung epithelium remains elusive. In this methods resource article, culture conditions to maintain three‐dimensional pulmonary tissue long‐term are reported and applied to recapitulate related diseases. Three‐dimensional human pulmonary tissue culture allows for investigation of hereditary diseases.
Analysis
This paper describes a method to establish long-term expanding human airway organoids from adult lung tissue for disease modeling.
Discovery
Mark T. Kozlowski; Christiana Crook; Hsun Teresa Ku
Fuyin Zheng; Yuminghao Xiao; Hui Liu; Yubo Fan; Ming Dao
Caleb Jensen; Yong Teng
Qirui Wu; Jinfeng Liu; Xiaohong Wang; Lingyan Feng; Jinbo Wu; Xiaoli Zhu; Weijia Wen; Xiuqing Gong
Giovanni Giuseppe Giobbe; Claire Crowley; Camilla Luni; Sara Campinoti; Moustafa Khedr; Kai Kretzschmar; Martina M. De Santis; Elisa Zambaiti; Federica Michielin; Laween Meran; Qianjiang Hu; Gijs J. F. van Son; Luca Urbani; Manfredi Anna; Monica Giomo; Simon Eaton; Davide Cacchiarelli; Vivian Li; Hans Clevers; Paola Bonfanti; Nicola Elvassore; Paolo De Coppi
Ruoshi Shi; Nikolina Radulovich; Christine Ng; Geoffrey Liu; Hirotsugu Notsuda; Michael Cabanero; Sebastião N. Martins-Filho; Vibha Raghavan; Quan Li; Arvind Singh Mer; Joshua C. Rosen; Ming Li; Yu-Hui Wang; Laura Tamblyn; Nhu‐An Pham; Benjamin Haibe‐Kains; Geoffrey Liu; Nadeem Moghal; Ming‐Sound Tsao
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