Human organoids: model systems for human biology and medicine

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(10), P. 571 - 584

Published: July 7, 2020

Language: Английский

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Organoids in cancer research

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(7), P. 407 - 418

Published: April 24, 2018

Language: Английский

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Organoid Modeling of the Tumor Immune Microenvironment

Cell, Journal Year: 2018, Volume and Issue: 175(7), P. 1972 - 1988.e16

Published: Dec. 1, 2018

Language: Английский

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Progress and potential in organoid research

Nature Reviews Genetics, Journal Year: 2018, Volume and Issue: 19(11), P. 671 - 687

Published: Sept. 18, 2018

Language: Английский

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Long‐term expanding human airway organoids for disease modeling

The EMBO Journal, Journal Year: 2019, Volume and Issue: 38(4)

Published: Jan. 14, 2019

Resource14 January 2019Open Access Transparent process Long-term expanding human airway organoids for disease modeling Norman Sachs Oncode Institute, Hubrecht Institute-KNAW and UMC Utrecht, The Netherlands Search more papers by this author Angelos Papaspyropoulos Domenique D Zomer-van Ommen Wilhelmina Children's Hospital Inha Heo Lena Böttinger Dymph Klay St. Antonius Nieuwegein, Fleur Weeber Cancer Amsterdam, Guizela Huelsz-Prince FOM Institute AMOLF, Nino Iakobachvili Maastricht University, Maastricht, Gimano Amatngalim Joep de Ligt orcid.org/0000-0002-0348-419X Arne van Hoeck orcid.org/0000-0002-6570-1452 Natalie Proost Mouse Clinic Aging (MCCA) Preclinical Intervention Unit, Marco C Viveen Anna Lyubimova Luc Teeven Sepideh Derakhshan Jeroen Korving Harry Begthel Johanna F Dekkers Kuldeep Kumawat Emilio Ramos Organoid Technology, Matthijs FM Oosterhout G Johan Offerhaus Dominique J Wiener Eduardo P Olimpio Krijn K Dijkstra Egbert Smit Maarten der Linden Sridevi Jaksani Marieke Ven Jos Jonkers orcid.org/0000-0002-9264-9792 Anne Rios Princess Máxima Center Pediatric Oncology, Emile E Voest Coline HM Moorsel Cornelis Ent Edwin Cuppen orcid.org/0000-0002-0400-9542 Alexander Oudenaarden Frank Coenjaerts Linde Meyaard Louis Bont Peter Peters Sander Tans S Zon Sylvia Boj Robert Vries Jeffrey M Beekman Hans Clevers Corresponding Author [email protected] orcid.org/0000-0002-3077-5582 Information Sachs1, Papaspyropoulos1, Ommen2, Heo1, Böttinger1, Klay3, Weeber4, Huelsz-Prince5, Iakobachvili6, Amatngalim2, Ligt7, Hoeck7, Proost8, Viveen7, Lyubimova1, Teeven1, Derakhshan2, Korving1, Begthel1, Dekkers1, Kumawat2, Ramos9, Oosterhout3, Offerhaus7, Wiener1, Olimpio5, Dijkstra4, Smit4, Linden2, Jaksani9, Ven8, Jonkers8, Rios10, Voest4, Moorsel3, Ent2, Cuppen7, Oudenaarden1, Coenjaerts7, Meyaard2, Bont2, Peters6, Tans5, Zon5, Boj9, Vries9, Beekman2 *,1,10 1Oncode 2Wilhelmina 3St. 4The 5FOM 6Maastricht 7UMC 8Mouse 9Hubrecht 10Princess *Corresponding author. Tel: +31 30 2121800; E-mail: EMBO Journal (2019)38:e100300https://doi.org/10.15252/embj.2018100300 See also: Paschini & CF Kim (February 2019) PDFDownload PDF of article text main figures. Peer ReviewDownload a summary the editorial decision including letters, reviewer comments responses to feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures Info Abstract Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects organ structure function. Here, we describe method establish long-term-expanding broncho-alveolar resections or lavage material. pseudostratified consist basal cells, functional multi-ciliated mucus-producing secretory CC10-secreting club cells. Airway derived cystic fibrosis (CF) patients allow assessment CFTR function in an organoid swelling assay. established lung cancer metastasis biopsies retain tumor histopathology as well gene mutations amenable drug screening. Respiratory syncytial virus (RSV) infection recapitulates central features, dramatically increases cell motility via non-structural viral NS2 protein, preferentially recruits neutrophils upon co-culturing. We conclude represent versatile models vitro study hereditary, malignant, infectious pulmonary disease. Synopsis To date, persistent culture adult epithelium remains elusive. In methods resource article, conditions maintain three-dimensional tissue long-term reported applied related diseases. Culture expansion healthy, hereditary malignant epithelial organoids. medium-throughput readily infection. Introduction several approaches have been explored generate mammalian (Barkauskas et al, 2017). 1993, Puchelle colleagues described first collagen (Benali 1993). A description generation iPS (induced pluripotent stem) was given Rossant included use CFTR-mutant proof concept (Wong 2012). Snoeck designed improved four-stage protocol (Huang 2014) later generated bud fetal development (Chen Spence (Dye 2015) followed modified trajectory mature organoids, containing basal, ciliated, These cultures were stable up months resembled proximal airways. Konishi al (2016) on cell-derived 3D, McCauley (2017) patient modeling. Hogan cell-based murine bronchiolar protocol, involving Matrigel supplemented with EGF (Rock 2009). Single isolated trachea grew into tracheospheres consisting ciliated luminal could be passaged at least twice. No club, neuroendocrine, observed study, clonal assay used demonstrate IL-6 treatment resulted formation expense (Tadokoro 2014). Tschumperlin combined primary bronchial fibroblasts, microvascular endothelial (Tan Under these conditions, randomly seeded mixed populations underwent rapid condensation self-organize discrete 4 weeks Hild Jaffe bronchospheres Mature composed mucin-producing (Hild Jaffe, 2016). Mou expanded mouse 2D allowed subsequent differentiation under air–liquid interphase conditions. And finally, Nikolic expand self-renewing Since none allows individuals vitro, set out such model variety Results Generation characterization collected macroscopically inconspicuous non-small-cell (NSCLC) undergoing medically indicated surgery through mechanical enzymatic disruption (see Materials Methods). Following our experience generating other tissues (Sato 2011; Karthaus 2014; 2015; Huch Wetering recent developments field (Mou 2016; Tadokoro Balasooriya 2017), embedded basement membrane extract (BME) activated/blocked signaling pathways important (Table EV1). optimized formed within days (94% success rate, n = 18). polarized, secretory, (Fig 1A B, Appendix Fig S1A, Movie EV1) termed (AOs). Cells stained marker keratin-5 (KRT5), secretoglobin family member 1 (SCGB1A1), cilia acetylated α-tubulin, mucin 5AC (MUC5AC) localized their corresponding vivo positions 1C, S1B). Secretory evidenced time-lapse microscopy showing beating whirling mucus (Movies EV2 EV3). Figure 1. Characterization Transmission electron micrograph AO cross section brush, Details display apical microvilli characteristic microtubule structure. Scale bars equal 10 μm, 2 500 nm. also S1A Movies EV1–EV3. Scanning partially opened visualizing its architecture, ultrastructure. surfaces 50 μm (overview) (details). Immunofluorescent sections AOs markers (acetylated α-tubulin), (MUC5AC), (SCGB1A1). KRT5 is present exclusively basally while cilia, MUC5AC, SCGB1A1 localize luminally. Counterstained actin cytoskeleton (red). bar equals μm. S1B IHC images. Luminescent viability comparing proliferative capacity two independently lines early, mid-, late passage numbers. Per group, 3,000 measured time points. Error standard deviations technical triplicates. Quantification types early (P5 vs. P19) determined immunofluorescence using markers. number does not differ significantly between AOs. Data shown representatives three independent experiments. indicate s.e.m. Download figure PowerPoint 1:2 1:4 ratios every week > year, proliferating comparable rates regardless 1D) retaining similar frequencies multi-ciliated, 1E, S1C). Comparative RNA sequencing confirmed findings dozens type-specific genes respective expression patterns (Appendix S1D E, Table EV2). composition validated quantitative PCR (qPCR): While expressing general NKX2-1 airway-specific markers, expressed virtually no HOXA5 [a bona fide mesenchyme (Hrycaj 2015)] alveolar transcripts S2A). transcriptomes strongly enriched bulk small signature S2B) enrichment analysis (GSEA), signatures limited S2C, Accordingly, hallmark encoding keratins, secretoglobins, dyneins, others consistently among highest S2D). Elevated levels WNT3A explained why AOs—in contrast intestinal 2011)—did require addition exogenous media. Manipulation WNT dramatic changes target S2E). Withdrawal Wnt amplifier R-spondin terminated after 3–4 passages S2E), withdrawal fibroblast growth factors S2F). Taken together, major characteristics epithelium. features swell modulation activation TMEM16A Rectal being successfully (CF; Noordhoek 2016), multi-organ extensive phenotypic variability caused transmembrane conductance regulator (CFTR; Ratjen 2015). opening channel cAMP-inducing agents (e.g., forskolin), anions fluid transported lumen resulting (Dekkers 2013), allowing personalized screenings current gold primarily affected interface (ALI) system lengthy protocols (Fulcher 2005). CFTR, considerably long (McCauley assess modeling, forskolin dose-dependent response largely, but entirely, abrogated chemical inhibition 2A, S3A), indicating presence additional ion channels. Indeed, AOs—but rectal organoids—swell Eact 2B, activator chloride (Namkung Sondo 2. Box-and-whisker plot concentration-dependent forskolin-induced absence inhibitors CFTRinh-172 GlyH101. Upon inhibition, noticeably decreased absent. Shown pooled data different each Whiskers smallest largest values, boxes 25th 75th percentile, horizontal solid line indicates median. AUC, area curve. Eact-induced AOs, (black outlines). Forskolin causes both (gray four Swelling linear h only S3A course plots. Representative histological periodic acid–Schiff (PAS)-stained CFTRF508del/F508del mutation. Note thick layer PAS-positive polysaccharides apically lining biopsies; lavages (BALs). S3B PAS-stained wild-type CFTRR334W/R334W sections. assays carrying (G542X premature stop associated severe protein; F508del most common mutation subjects severely reduces trafficking function, leading (high sweat chloride, high pancreas insufficiency, pseudomonas rate); R334W milder lower sufficiency reduced conductivity, normal expression, some residual function). Forskolin-induced rarely exceeds vehicle control

Language: Английский

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Engineering organoids

Nature Reviews Materials, Journal Year: 2021, Volume and Issue: 6(5), P. 402 - 420

Published: Feb. 19, 2021

Language: Английский

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Tales from the crypt: new insights into intestinal stem cells

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2018, Volume and Issue: 16(1), P. 19 - 34

Published: Nov. 14, 2018

Language: Английский

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Targeting metastatic cancer

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(1), P. 34 - 44

Published: Jan. 1, 2021

Language: Английский

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Cancer modeling meets human organoid technology

Science, Journal Year: 2019, Volume and Issue: 364(6444), P. 952 - 955

Published: June 6, 2019

Organoids are microscopic self-organizing, three-dimensional structures that grown from stem cells in vitro. They recapitulate many structural and functional aspects of their vivo counterpart organs. This versatile technology has led to the development novel human cancer models. It is now possible create indefinitely expanding organoids starting tumor tissue individuals suffering a range carcinomas. Alternatively, CRISPR-based gene modification allows engineering organoid models through introduction any combination alterations normal organoids. When combined with immune fibroblasts, become for microenvironment enabling immune-oncology applications. Emerging evidence indicates can be used accurately predict drug responses personalized treatment setting. Here, we review current state future prospects rapidly evolving field.

Language: Английский

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An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(5), P. 838 - 849

Published: April 22, 2019

Language: Английский

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