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Long-term expanding human airway organoids for disease modeling.
The EMBO Journal ( IF 9.4 ) Pub Date : 2019-01-14 , DOI: 10.15252/embj.2018100300 Norman Sachs 1 , Angelos Papaspyropoulos 1 , Domenique D Zomer-van Ommen 2 , Inha Heo 1 , Lena Böttinger 1 , Dymph Klay 3 , Fleur Weeber 4 , Guizela Huelsz-Prince 5 , Nino Iakobachvili 6 , Gimano D Amatngalim 2 , Joep de Ligt 7 , Arne van Hoeck 7 , Natalie Proost 8 , Marco C Viveen 7 , Anna Lyubimova 1 , Luc Teeven 1 , Sepideh Derakhshan 2 , Jeroen Korving 1 , Harry Begthel 1 , Johanna F Dekkers 1 , Kuldeep Kumawat 2 , Emilio Ramos 9 , Matthijs Fm van Oosterhout 3 , G Johan Offerhaus 7 , Dominique J Wiener 1 , Eduardo P Olimpio 5 , Krijn K Dijkstra 4 , Egbert F Smit 4 , Maarten van der Linden 2 , Sridevi Jaksani 9 , Marieke van de Ven 8 , Jos Jonkers 8 , Anne C Rios 10 , Emile E Voest 4 , Coline Hm van Moorsel 3 , Cornelis K van der Ent 2 , Edwin Cuppen 7 , Alexander van Oudenaarden 1 , Frank E Coenjaerts 7 , Linde Meyaard 2 , Louis J Bont 2 , Peter J Peters 6 , Sander J Tans 5 , Jeroen S van Zon 5 , Sylvia F Boj 9 , Robert G Vries 9 , Jeffrey M Beekman 2 , Hans Clevers 10, 11
The EMBO Journal ( IF 9.4 ) Pub Date : 2019-01-14 , DOI: 10.15252/embj.2018100300 Norman Sachs 1 , Angelos Papaspyropoulos 1 , Domenique D Zomer-van Ommen 2 , Inha Heo 1 , Lena Böttinger 1 , Dymph Klay 3 , Fleur Weeber 4 , Guizela Huelsz-Prince 5 , Nino Iakobachvili 6 , Gimano D Amatngalim 2 , Joep de Ligt 7 , Arne van Hoeck 7 , Natalie Proost 8 , Marco C Viveen 7 , Anna Lyubimova 1 , Luc Teeven 1 , Sepideh Derakhshan 2 , Jeroen Korving 1 , Harry Begthel 1 , Johanna F Dekkers 1 , Kuldeep Kumawat 2 , Emilio Ramos 9 , Matthijs Fm van Oosterhout 3 , G Johan Offerhaus 7 , Dominique J Wiener 1 , Eduardo P Olimpio 5 , Krijn K Dijkstra 4 , Egbert F Smit 4 , Maarten van der Linden 2 , Sridevi Jaksani 9 , Marieke van de Ven 8 , Jos Jonkers 8 , Anne C Rios 10 , Emile E Voest 4 , Coline Hm van Moorsel 3 , Cornelis K van der Ent 2 , Edwin Cuppen 7 , Alexander van Oudenaarden 1 , Frank E Coenjaerts 7 , Linde Meyaard 2 , Louis J Bont 2 , Peter J Peters 6 , Sander J Tans 5 , Jeroen S van Zon 5 , Sylvia F Boj 9 , Robert G Vries 9 , Jeffrey M Beekman 2 , Hans Clevers 10, 11
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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.
中文翻译：
用于疾病建模的长期扩展的人类气道类器官。
类器官是从干细胞生长而来的自组织 3D 结构，概括了器官结构和功能的基本方面。在这里，我们描述了一种从支气管肺泡切除或灌洗材料中建立长期扩张的人类气道类器官的方法。假复层气道类器官由基底细胞、功能性多纤毛细胞、粘液分泌细胞和 CC10 分泌棒细胞组成。来自囊性纤维化 (CF) 患者的气道类器官可以在类器官肿胀测定中评估 CFTR 功能。通过肺癌切除和转移活检建立的类器官保留了肿瘤组织病理学以及癌症基因突变，并且适合药物筛选。呼吸道合胞病毒 (RSV) 感染重现了核心疾病特征，通过非结构病毒 NS2 蛋白显着增加类器官细胞运动性，并在共培养时优先招募中性粒细胞。我们得出的结论是，人类气道类器官代表了遗传性、恶性和传染性肺部疾病体外研究的通用模型。
更新日期：2020-03-19
中文翻译：
用于疾病建模的长期扩展的人类气道类器官。
类器官是从干细胞生长而来的自组织 3D 结构，概括了器官结构和功能的基本方面。在这里，我们描述了一种从支气管肺泡切除或灌洗材料中建立长期扩张的人类气道类器官的方法。假复层气道类器官由基底细胞、功能性多纤毛细胞、粘液分泌细胞和 CC10 分泌棒细胞组成。来自囊性纤维化 (CF) 患者的气道类器官可以在类器官肿胀测定中评估 CFTR 功能。通过肺癌切除和转移活检建立的类器官保留了肿瘤组织病理学以及癌症基因突变，并且适合药物筛选。呼吸道合胞病毒 (RSV) 感染重现了核心疾病特征，通过非结构病毒 NS2 蛋白显着增加类器官细胞运动性，并在共培养时优先招募中性粒细胞。我们得出的结论是，人类气道类器官代表了遗传性、恶性和传染性肺部疾病体外研究的通用模型。
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