Long-term expanding human airway organoids for disease modeling
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 F.M. 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 H.M. 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.J. Vries,Jeffrey M. Beekman,Hans Clevers +47 more
TLDR
It is concluded that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.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.read more
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SARS-CoV-2 productively infects human gut enterocytes.
Mart M. Lamers,Joep Beumer,Jelte van der Vaart,Kèvin Knoops,Jens Puschhof,Tim I Breugem,Raimond B. G. Ravelli,J. Paul van Schayck,Anna Z Mykytyn,Hans Duimel,Elly van Donselaar,Samra Riesebosch,Helma J.H. Kuijpers,Debby Schipper,Willine J. van de Wetering,Miranda de Graaf,Marion Koopmans,Edwin Cuppen,Peter J. Peters,Bart L. Haagmans,Hans Clevers +20 more
TL;DR: It is demonstrated that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut, and hSIOs serve as an experimental model for coronavirus infection and biology.
Journal ArticleDOI
Human organoids: model systems for human biology and medicine.
TL;DR: The applications, advantages and disadvantages of human organoids as models of development and disease and the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments are discussed.
Journal ArticleDOI
Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids
Krijn K. Dijkstra,Chiara M Cattaneo,Fleur Weeber,Myriam Chalabi,Joris van de Haar,Lorenzo F. Fanchi,Maarten Slagter,Daphne L. van der Velden,Sovann Kaing,Sander Kelderman,Nienke van Rooij,Monique E. van Leerdam,Annekatrien Depla,Egbert F. Smit,Koen J. Hartemink,Rosa de Groot,Monika C. Wolkers,Norman Sachs,Petur Snaebjornsson,Kim Monkhorst,John B. A. G. Haanen,Hans Clevers,Ton N. Schumacher,Emile E. Voest +23 more
TL;DR: A platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner is established and co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer.
Journal ArticleDOI
Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
Bo Meng,Adam Abdullahi,Isabella Ferreira,Niluka Goonawardane,Akatsuki Saito,Izumi Kimura,Daichi Yamasoba,P. P. G. Gerber,Saman Fatihi,Surabhi Rathore,Samantha K. Zepeda,Guido Papa,Steven Kemp,Terumasa Ikeda,Mako Toyoda,Toong Seng Tan,Jin Kuramochi,Shigeki Mitsunaga,Takamasa Ueno,Kotaro Shirakawa,Akifumi Takaori-Kondo,Teresa Brevini,Donna L. Mallery,Oscar Charles,Stephen Baker,Gordon Dougan,Christoph Hess,Nathalie Kingston,Paul J. Lehner,Paul A. Lyons,Nick Matheson,Willem H. Ouwehand,Caroline M. Saunders,Charlotte Summers,James Thaventhiran,Mark Toshner,Michael P. Weekes,Patrick Maxwell,Ashley Shaw,Ashlea Bucke,Jo Calder,Laura Canna,Jason Domingo,Anne Elmer,Stewart Fuller,Julie Harris,Sarah Hewitt,Jane Kennet,Sherly Jose,Jenny Kourampa,Anne Meadows,Criona O’Brien,Jane Mary Price,Cherry Publico,Rebecca Rastall,Carla Ribeiro,Jane Rowlands,Valentina Ruffolo,Hugo Tordesillas,Ben Bullman,Benjamin J. Dunmore,Stefan Gräf,Joshua Hodgson,Christopher Huang,K Hunter,Emma Jones,Ekaterina Legchenko,Cecilia Cabrera Matara,Jennifer M. Martin,Federica Mescia,Ciara O’Donnell,Linda Pointon,Joy Shih,Rachel Sutcliffe,Tobias Tilly,Carmen M. Treacy,Zhen Tong,Jennifer Wood,Marta Wylot,Ariana Betancourt,Georgie Bower,Chiara Cossetti,Aloka De Sa,Maddie Epping,Stuart Fawke,Nicholas Gleadall,Richard Grenfell,Andrew Hinch,Sarah Jackson,Isobel Jarvis,Ben Krishna,Francesca L. Nice,Ommar Omarjee,Marianne Perera,Martin Potts,Nathan Richoz,Veronika Romashova,Luca Stefanucci,Mateusz Strezlecki,Lori Turner,E. D. De Bie,Katherine Bunclark,Masa Josipovic,Michael Mackay,Helen Butcher,Dan Scott Caputo,Mathew Allen. Chandler,Patrick F. Chinnery,Debbie Clapham-Riley,E Dewhurst,Christian Fernandez,Anita Furlong,Barbara J. Graves,J. Gray,Sabine Hein,Tasmin Ivers,Emma Le Gresley,Rachel Linger,Mary A Kasanicki,Rebecca King,Sara E. Meloy,Alex A. Moulton,Frances E. Muldoon,Nigel R. Ovington,Sofia Papadia,Christopher J. Penkett,Isabel Phelan,Venkatesh-Prasad Ranganath,R. Paraschiv,Abigail Sage,Jennifer G. Sambrook,Ingrid Scholtes,Katherine Schon,Hannah Stark,Kathleen Stirrups,Paul Townsend,Neil Walker,Jennifer Rose Webster,Erika P. Butlertanaka,Yurie Tanaka,Jumpei Ito,Keiya Uriu,Yusuke Kosugi,Mai Suganami,Akiko Oide,Miyabishara Yokoyama,Mika Chiba,Chihiro Motozono,Hesham Nasser,Ryo Shimizu,K. Kitazato,Haruyo Hasebe,Takashi Irie,So Nakagawa,Jiaqi Wu,Miyoko Takahashi,Takasuke Fukuhara,Kenta Shimizu,Kana Tsushima,Haruko Kubo,Yasuhiro Kazuma,Ryosuke Nomura,Yoshihito Horisawa,Kayoko Nagata,Yugo Kawai,Yohei Yanagida,Yusuke Tashiro,Kenzo Tokunaga,Seiya Ozono,Ryoko Kawabata,Nanami Morizako,Kenji Sadamasu,Hiroyuki Asakura,Mami Nagashima,Kazuhisa Yoshimura,Paul Cardenas,E. Muñoz,Veronica Barragan,Sully Márquez,Belén Prado-Vivar,Mónica Becerra-Wong,Mateo Caravajal,Gabriel Trueba,Patricio Rojas-Silva,Michelle Grunauer,Bernardo Gutierrez,Juan José Guadalupe,Juan Carlos Fernandez-Cadena,D. Andrade-Molina,Manuel E. Baldeón,Andrea Pinos,John E. Bowen,Anshu Joshi,Alexandra C. Walls,Laurelle Jackson,Darren Martin,Kenneth G. C. Smith,John S. Bradley,John A. G. Briggs,Jin W. Choi,Elo Madissoon,Kerstin B. Meyer,Petra Mlcochova,Lourdes Ceron-Gutierrez,Rainer Doffinger,Sarah A. Teichmann,Andrew J. Fisher,Matteo Samuele Pizzuto,Anna De Marco,Davide Corti,Myra Hosmillo,Joo-Hyeon Lee,Leo C. James,Lipi Thukral,David Veesler,Alex Sigal,Fotios Sampaziotis,Ian Goodfellow,Kei Sato,Ravindra K. Gupta +219 more
TL;DR: The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein this paper , which increased the evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses.
Journal ArticleDOI
Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity
Bo Meng,Adam Abdullahi,Isabella Ferreira,Niluka Goonawardane,Akatsuki Saito,Izumi Kimura,Daichi Yamasoba,P. P. G. Gerber,Saman Fatihi,Surabhi Rathore,Samantha K. Zepeda,Guido Papa,Steven Kemp,Terumasa Ikeda,Mako Toyoda,Toong Seng Tan,Jin Kuramochi,Shigeki Mitsunaga,Takamasa Ueno,Kotaro Shirakawa,Akifumi Takaori-Kondo,Teresa Brevini,Donna L. Mallery,Oscar Charles,John E. Bowen,Anshu Joshi,Alexandra C. Walls,Laurelle Jackson,Darren Martin,Ken C. Smith,John S. Bradley,John A. G. Briggs,Jin W. Choi,Elo Madissoon,Kerstin Meyer,Petra Mlcochova,Lourdes Ceron-Gutierrez,Rainer Doffinger,Sarah A. Teichmann,Andrew J. Fisher,Matteo Samuele Pizzuto,Anna De Marco,Davide Corti,Myra Hosmillo,Joo-Hyeon Lee,Leo C. James,Lipi Thukral,David Veesler,Alex Sigal,Fotios Sampaziotis,Ian Goodfellow,Nick Matheson,Kei Sato,Ravindra K. Gupta,The CITIID-NIHR BioResource COVID-19 Collaboration,The Genotype to Phenotype Japan Consortium,Ecuador-COVID19 Consortium +56 more
TL;DR: In this article , the SARS-CoV-2 Omicron BA has multiple mutations in its spike protein, which increases evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses.
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