{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:18:36Z","timestamp":1790313516818,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The primary role of the parathyroid glands is to maintain calcium homeostasis through the secretion of parathyroid hormone (PTH). The limited proliferative capacity and differentiation of parathyroid cells hinder the generation of cell therapy options. In this study, parathyroid organoids are successfully generated from human\u2010induced pluripotent stem cells (hiPSCs). At the end of the 20 days of differentiation, the parathyroid organoids exhibited distinct parathyroid morphology. Stereomicroscope, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis demonstrated the 3D arrangement of the cell layers in which intracellular structures of parathyroid cells resemble human parathyroid cellular morphology. Comprehensive molecular analyses, including RNA sequencing (RNA\u2010Seq) and liquid chromatography\/mass spectrometry (LC\u2010MS\/MS), confirmed the expression of key parathyroid\u2010related markers. Protein expression of CasR, CxCr4, Gcm2, and PTH are observed in parathyroid organoids. Parathyroid organoids secrete PTH, demonstrate active intercellular calcium signaling, and induce osteogenic differentiation via their secretome. The tissue integration potential of parathyroid organoids is determined by transplantation into parathyroidectomized rats. The organoid transplanted animals showed significant elevations in PTH\u2010related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid\u2010transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH\u2010related diseases, including hypoparathyroidism.<\/jats:p>","DOI":"10.1002\/advs.202407567","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T17:04:13Z","timestamp":1727456653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Induced Pluripotent Stem Cell\u2010Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function"],"prefix":"10.1002","volume":"11","author":[{"given":"Selinay","family":"\u015eenkal\u2010Turhan","sequence":"first","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezgi","family":"Bulut\u2010Okumu\u015f","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhterem","family":"Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Department of Veterinary Obstetrics and Gynecology Faculty of Veterinary Medicine University of F\u0131rat  Elaz\u0131\u011f 23119 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ne\u015fe","family":"Ba\u015fak T\u00fcrkmen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology Faculty of Pharmacy University of Inonu  Malatya 44280 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"Ta\u015fl\u0131dere","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology Faculty of Medicine University of Inonu  Malatya 44280 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fikrettin","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eahin","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u0131nar","family":"Akku\u015f S\u00fct","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4160-2270","authenticated-orcid":false,"given":"Ay\u015feg\u00fcl","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Genetics and Bioengineering Faculty of Engineering Yeditepe University  \u0130stanbul 34755 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386456-7.03708-4"},{"key":"e_1_2_8_2_1","volume-title":"Physiology, Parathyroid Hormone (PTH)","author":"Khan M.","year":"2018"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3366"},{"key":"e_1_2_8_4_1","author":"Lofrese J. J.","year":"2023","journal-title":"StatPearls"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E19-03-0135"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00120.2020"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118570"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.07.050"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0259-3"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1471-y"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1058846"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2008.0337"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13634"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0030-6665(02)00129-9"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0803050"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2008.12.026"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.21037\/gs.2017.09.15"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1680417"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.06.044"},{"key":"e_1_2_8_21_1","first-page":"0170","volume":"17","author":"Ignatoski K. M. W.","year":"2011","journal-title":"Tissue Engineering Part C: Methods"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.21666"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.09.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00333-1"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210662"},{"key":"e_1_2_8_26_1","volume-title":"Physiology, Parathyroid Hormone (PTH)","author":"Khan M.","year":"2018"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/35018111"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406116101"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","unstructured":"G. A.Block K. J.Martin B.Ch A. L. M.De Francisco S. A.Turner M. M.Avram M. G.Suranyi G.Hercz J.Cunningham A. K.Abu\u2010Alfa P.Messa D. W.Coyne F.Locatelli R. M.Cohen P.Evenepoel S. M.Moe A.Fournier J.Braun L. C.Mccary J.Zani K. A.Olson T. B.Dr\u00fceke W. G.Goodman Cinacalcet for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis 2004.","DOI":"10.1056\/NEJMoa031633"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e3181671b61"},{"key":"e_1_2_8_31_1","volume":"10","author":"Kim H. Y.","year":"2022","journal-title":"Biomedicines"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.06.211"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)62473-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12124"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2015.045"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.154"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2017.0067"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-013-0472-z"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2021.02.033"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8111443"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20201165"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-006-0687-y"},{"key":"e_1_2_8_44_1","doi-asserted-by":"crossref","unstructured":"A.Dobin T. R.Gingeras Curr Protoc Bioinformatics2015 51 11.14. 1.","DOI":"10.1002\/0471250953.bi1114s51"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv468"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0611-3"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-021-00190-1"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1106"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.772403"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0128-8"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.029"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100696"},{"key":"e_1_2_8_58_1","first-page":"239","volume":"24","author":"Kohen M. C.","year":"2018","journal-title":"Mol Vis"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-020-00968-2"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10281-0"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8935-5_33"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-022-00529-z"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202407567","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:24:30Z","timestamp":1759785870000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202407567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":62,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/advs.202407567"],"URL":"https:\/\/doi.org\/10.1002\/advs.202407567","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"2024-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2407567"}}