{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:59:23Z","timestamp":1788184763249,"version":"build-2803163510"},"reference-count":38,"publisher":"Institute of Physiology of the Czech Academy of Sciences","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiol Res"],"abstract":"<jats:p>Organoids are complex multicellular structures that stem cells self-organize in three-dimensional (3D) cultures into anatomical structures and functional units similar to those seen in the organs from which they originate. This review describes the construction of thyroid organoids and the research progress that has occurred in models of thyroid-related disease. As a novel tool for modeling in a 3D multicellular environment, organoids help provide some useful references for the study of the pathogenesis of thyroid disease.<\/jats:p>","DOI":"10.33549\/physiolres.935102","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:39:27Z","timestamp":1700663967000},"page":"557-564","source":"Crossref","is-referenced-by-count":4,"title":["Advances in the Construction and Application of Thyroid Organoids"],"prefix":"10.33549","volume":"72","author":[{"given":"Y","family":"ZHANG","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"FU","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"WANG","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"SUN","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"19169","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"1.\tKurmann AA, Serra M, Hawkins F, Rankin SA, Mori M, Astapova I, Ullas S, ET AL. Regeneration of thyroid function by transplantation of differentiated pluripotent stem cells. Cell Stem Cell 2015;17:527-542. https:\/\/doi.org\/10.1016\/j.stem.2015.09.004","DOI":"10.1016\/j.stem.2015.09.004"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"2.\tSato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, ET AL. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262-265. https:\/\/doi.org\/10.1038\/nature07935","DOI":"10.1038\/nature07935"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"3.\tLi M, Izpisua Belmonte JC. Organoids - preclinical models of human disease. N Engl J Med 2019;380:569-579. https:\/\/doi.org\/10.1056\/NEJMra1806175","DOI":"10.1056\/nejmra1806175"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"4.\tTaylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM, Okosieme OE. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018;14:301-316. https:\/\/doi.org\/10.1038\/nrendo.2018.18","DOI":"10.1530\/ey.15.3.16"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"5.\tDuval K, Grover H, Han LH, Mou Y, Pegoraro AF, Fredberg J, Chen Z. Modeling physiological events in 2D vs. 3D cell culture. Physiology (Bethesda) 2017;32:266-277. https:\/\/doi.org\/10.1152\/physiol.00036.2016","DOI":"10.1152\/physiol.00036.2016"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"6.\tAntonica F, Kasprzyk DF, Opitz R, Iacovino M, Liao XH, Dumitrescu AM, Refetoff S, ET AL. Generation of functional thyroid from embryonic stem cells. Nature 2012;491:66-71. https:\/\/doi.org\/10.1038\/nature11525","DOI":"10.1038\/nature11525"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"7.\tSamimi H, Atlasi R, Parichehreh-Dizaji S, Khazaei S, Akhavan Rahnama M, Seifirad S, Haghpanah V. A systematic review on thyroid organoid models: time-trend and its achievements. Am J Physiol Endocrinol Metab 2021;320:E581-E590. https:\/\/doi.org\/10.1152\/ajpendo.00479.2020","DOI":"10.1152\/ajpendo.00479.2020"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"8.\tDame K, Cincotta S, Lang AH, Sanghrajka RM, Zhang L, Choi J, Kwok L, ET AL. Thyroid progenitors are robustly derived from embryonic stem cells through transient, developmental stage-specific overexpression of Nkx2-1. Stem Cell Reports 2017;8:216-225. https:\/\/doi.org\/10.1016\/j.stemcr.2016.12.024","DOI":"10.1016\/j.stemcr.2016.12.024"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"9.\tMa R, Morshed SA, Latif R, Davies TF. Thyroid cell differentiation from murine induced pluripotent stem cells. Front Endocrinol (Lausanne) 2015;6:56. https:\/\/doi.org\/10.3389\/fendo.2015.00056","DOI":"10.3389\/fendo.2015.00056"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"10.\tMa R, Latif R, Davies TF. Human embryonic stem cells form functional thyroid follicles. Thyroid 2015;25:455-461. https:\/\/doi.org\/10.1089\/thy.2014.0537","DOI":"10.1089\/thy.2014.0537"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"11.\tOgundipe VML, Groen AH, Hosper N, Nagle PWK, Hess J, Faber H, Jellema AL, ET AL. Generation and differentiation of adult tissue-derived human thyroid organoids. Stem Cell Reports 2021;16:913-925. https:\/\/doi.org\/10.1016\/j.stemcr.2021.02.011","DOI":"10.1530\/ey.18.3.3"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"12.\tLiang J, Qian J, Yang L, Chen X, Wang X, Lin X, Wang X, Zhao B. Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture. Adv Sci (Weinh) 2022;9:e2105568. https:\/\/doi.org\/10.1002\/advs.202105568","DOI":"10.1002\/advs.202105568"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"13.\tLongmire TA, Ikonomou L, Hawkins F, Christodoulou C, Cao Y, Jean JC, Kwok LW, ET AL. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell 2012;10:398-411. https:\/\/doi.org\/10.1016\/j.stem.2012.01.019","DOI":"10.1016\/j.stem.2012.01.019"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"14.\tDom G, Dmitriev P, Lambot MA, Van Vliet G, Glinoer D, Libert F, Lefort A, Dumont JE, Maenhaut C. Transcriptomic signature of human embryonic thyroid reveals transition from differentiation to functional maturation. Front Cell Dev Biol 2021;9:669354. https:\/\/doi.org\/10.3389\/fcell.2021.669354","DOI":"10.1530\/ey.19.3.4"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"15.\tSj\u00f6lin G, Holmberg M, T\u00f6rring O, Bystr\u00f6m K, Khamisi S, de Laval D, Abraham-Nordling M, ET AL. The long-term outcome of treatment for Graves' hyperthyroidism. Thyroid 2019;29:1545-1557. https:\/\/doi.org\/10.1089\/thy.2019.0085","DOI":"10.1089\/thy.2019.0085"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"16.\tvan der Vaart J, Bosmans L, Sijbesma SF, Knoops K, van de Wetering WJ, Otten HG, Begthel H, ET AL. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves' hyperthyroidism. Proc Natl Acad Sci U S A 2021;118:e2117017118. https:\/\/doi.org\/10.1073\/pnas.2117017118","DOI":"10.1073\/pnas.2117017118"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"17.\tIchioka H, Ida Y, Watanabe M, Ohguro H, Hikage F. Prostaglandin F2\u03b1 and EP2 agonists, and a ROCK inhibitor modulate the formation of 3D organoids of Grave's orbitopathy related human orbital fibroblasts. Exp Eye Res 2021;205:108489. https:\/\/doi.org\/10.1016\/j.exer.2021.108489","DOI":"10.1016\/j.exer.2021.108489"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"18.\tDew R, Okosieme O, Dayan C, Eligar V, Khan I, Razvi S, Pearce S, Wilkes S. Clinical, behavioural and pharmacogenomic factors influencing the response to levothyroxine therapy in patients with primary hypothyroidism-protocol for a systematic review. Syst Rev 2017;6:60. https:\/\/doi.org\/10.1186\/s13643-017-0457-z","DOI":"10.1186\/s13643-017-0457-z"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"19.\tWatt T, Cramon P, Heged\u00fcs L, Bjorner JB, Bonnema SJ, Rasmussen \u00c5 K, Feldt-Rasmussen U, Groenvold M. The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. J Clin Endocrinol Metab 2014;99:3708-3717. https:\/\/doi.org\/10.1210\/jc.2014-1322","DOI":"10.1210\/jc.2014-1322"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"20.\tRomitti M, Tourneur A, de Faria da Fonseca B, Doumont G, Gillotay P, Liao XH, Eski SE, ET AL. Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism. Nat Commun 2022;13:7057. https:\/\/doi.org\/10.1038\/s41467-022-34776-7","DOI":"10.1530\/ey.20.1.4"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"21.\tKim S, Park YW, Schiff BA, Doan DD, Yazici Y, Jasser SA, Younes M, ET AL. An orthotopic model of anaplastic thyroid carcinoma in athymic nude mice. Clin Cancer Res 2005;11:1713-1721. https:\/\/doi.org\/10.1158\/1078-0432.CCR-04-1908","DOI":"10.1158\/1078-0432.ccr-04-1908"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"22.\tJian M, Ren L, He G, Lin Q, Tang W, Chen Y, Chen J, ET AL. A novel patient-derived organoids-based xenografts model for preclinical drug response testing in patients with colorectal liver metastases. J Transl Med 2020;18:234. https:\/\/doi.org\/10.1186\/s12967-020-02407-8","DOI":"10.1186\/s12967-020-02407-8"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"23.\tJankovic J, Dettwiler M, Fern\u00e1ndez MG, Ti\u00e8che E, Hahn K, April-Monn S, Dettmer MS, ET AL. Validation of immunohistochemistry for canine proteins involved in thyroid iodine uptake and their expression in canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-derived organoids. Vet Pathol 2021;58:1172-1180. https:\/\/doi.org\/10.1177\/03009858211018813","DOI":"10.1177\/03009858211018813"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"24.\tChen D, Tan Y, Li Z, Li W, Yu L, Chen W, Liu Y, ET AL. Organoid cultures derived from patients with papillary thyroid cancer. J Clin Endocrinol Metab 2021;106:1410-1426. https:\/\/doi.org\/10.1210\/clinem\/dgab020","DOI":"10.1210\/clinem\/dgab020"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"25.\tChen D, Su X, Zhu L, Jia H, Han B, Chen H, Liang Q, ET AL. Papillary thyroid cancer organoids harboring BRAF(V600E) mutation reveal potentially beneficial effects of BRAF inhibitor-based combination therapies. J Transl Med 2023;21:9. https:\/\/doi.org\/10.1186\/s12967-022-03848-z","DOI":"10.1186\/s12967-022-03848-z"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"26.\tPecce V, Sponziello M, Bini S, Grani G, Durante C, Verrienti A. Establishment and maintenance of thyroid organoids from human cancer cells. STAR Protoc 2022;3:101393. https:\/\/doi.org\/10.1016\/j.xpro.2022.101393","DOI":"10.1016\/j.xpro.2022.101393"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"27.\tLai X, Xia Y, Zhang B, Li J, Jiang Y. A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk. Oncotarget 2017;8:62414-62424. https:\/\/doi.org\/10.18632\/oncotarget.18620","DOI":"10.18632\/oncotarget.18620"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"28.\tHe X, Xiong C, Liu A, Zhao W, Xia X, Peng S, Li C, ET AL. Phagocytosis deficiency of macrophages in NOD.H-2(h4) mice accelerates the severity of iodine-induced autoimmune thyroiditis. Biol Trace Elem Res 2018;184:196-205. https:\/\/doi.org\/10.1007\/s12011-017-1183-z","DOI":"10.1007\/s12011-017-1183-z"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"29.\tWang X, Liu H, Zhang Y, Li J, Teng X, Liu A, Yu X, Shan Z, Teng W. Effects of isolated positive maternal thyroglobulin antibodies on brain development of offspring in an experimental autoimmune thyroiditis model. Thyroid 2015;25:551-558. https:\/\/doi.org\/10.1089\/thy.2014.0310","DOI":"10.1089\/thy.2014.0310"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"30.\tVilgelm AE, Bergdorf K, Wolf M, Bharti V, Shattuck-Brandt R, Blevins A, Jones C, ET AL. Fine-needle aspiration-based patient-derived cancer organoids. iScience 2020;23:101408. https:\/\/doi.org\/10.1016\/j.isci.2020.101408","DOI":"10.1016\/j.isci.2020.101408"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"31.\tXiao H, Liang J, Liu S, Zhang Q, Xie F, Kong X, Guo S, ET AL. Proteomics and organoid culture reveal the underlying pathogenesis of hashimoto's thyroiditis. Front Immunol 2021;12:784975. https:\/\/doi.org\/10.3389\/fimmu.2021.784975","DOI":"10.3389\/fimmu.2021.784975"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"32.\tShin W, Wu A, Min S, Shin YC, Fleming RYD, Eckhardt SG, Kim HJ. Spatiotemporal gradient and instability of Wnt induce heterogeneous growth and differentiation of human intestinal organoids. iScience 2020;23:101372. https:\/\/doi.org\/10.1016\/j.isci.2020.101372","DOI":"10.1016\/j.isci.2020.101372"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"33.\tSerex L, Sharma K, Rizov V, Bertsch A, McKinney JD, Renaud P. Microfluidic-assisted bioprinting of tissues and organoids at high cell concentrations. Biofabrication 2021;13. https:\/\/doi.org\/10.1088\/1758-5090\/abca80","DOI":"10.1088\/1758-5090\/abca80"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"34.\tRiley A, Green V, Cheah R, McKenzie G, Karsai L, England J, Greenman J. A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform. BMC Cancer 2019;19:259. https:\/\/doi.org\/10.1186\/s12885-019-5465-z","DOI":"10.1186\/s12885-019-5465-z"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"35.\tHe A, Powell S, Kyle M, Rose M, Masmila E, Estrada V, Sicklick JK, Molinolo A, Kaushal S. Cryopreservation of viable human tissues: Renewable resource for viable tissue, cell lines, and organoid development. Biopreserv Biobank 2020;18:222-227. https:\/\/doi.org\/10.1089\/bio.2019.0062","DOI":"10.1089\/bio.2019.0062"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"36.\tK\u00fchnlenz J, Karwelat D, Steger-Hartmann T, Raschke M, Bauer S, Vural \u00d6, Marx U, Tinwell H, Bars R. A microfluidic thyroid-liver platform to assess chemical safety in humans. Altex 2023;40:61-82. https:\/\/doi.org\/10.14573\/altex.2108261","DOI":"10.14573\/altex.2108261"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"37.\tSpaletta G, Sofroniou M, Barbaro F, Di Conza G, Mosca S, Toni R. A computational template for 3D modelling of the vascular scaffold of the human thyroid gland. Tissue Eng Part A 2023;29:47-57. https:\/\/doi.org\/10.1089\/ten.TEA.2022.0148","DOI":"10.1089\/ten.tea.2022.0148"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"38.\tRiley A, Jones H, England J, Kuvshinov D, Green V, Greenman J. Identification of soluble tissue-derived biomarkers from human thyroid tissue explants maintained on a microfluidic device. Oncol Lett 2021;22:780. https:\/\/doi.org\/10.3892\/ol.2021.13041","DOI":"10.3892\/ol.2021.13041"}],"container-title":["Physiological Research"],"original-title":[],"language":"en","deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:39:42Z","timestamp":1700663982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.biomed.cas.cz\/physiolres\/pdf\/2023\/72_557.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,11,15]]}},"URL":"https:\/\/doi.org\/10.33549\/physiolres.935102","relation":{},"ISSN":["1802-9973","0862-8408"],"issn-type":[{"value":"1802-9973","type":"electronic"},{"value":"0862-8408","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11,20]]}}}