Induced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function

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dc.contributor.authorSenkal-Turhan, Selinay
dc.contributor.authorBulut-Okumus, Ezgi
dc.contributor.authorAydin, Muhterem
dc.contributor.authorTurkmen, Nese Basak
dc.contributor.authorTaslidere, Asli
dc.contributor.authorSahin, Fikrettin
dc.contributor.authorYilmaz, Sahin
dc.date.accessioned2026-04-04T13:37:45Z
dc.date.available2026-04-04T13:37:45Z
dc.date.issued2024
dc.departmentİnönü Üniversitesi
dc.description.abstractThe 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-induced 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-Seq) and liquid chromatography/mass spectrometry (LC-MS/MS), confirmed the expression of key parathyroid-related 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-related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid-transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH-related diseases, including hypoparathyroidism. iPSC-derived parathyroid organoids express PTH-related markers at the protein and gene levels. The transplantation of parathyroid organoids into parathyroidectomized rats shows their functional activity and tissue integration capability. iPSC-derived parathyroid organoids successfully release PTH both in vitro and in vivo. Parathyroid organoid technology may improve defective parathyroid function and related diseases. image
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [219S665]; TUBITAK [2211-C]; Turkish Academy of Sciences Outstanding Young Scientists Award [TBA-GEBIdot;P 2020]; Yeditepe University Writing Center
dc.description.sponsorshipThis study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 219S665. The authors thank TUBITAK for their support. Ay & scedil;eguel Do & gbreve;an was supported by Turkish Academy of Sciences Outstanding Young Scientists Award (TUEBA-GEB & Idot;P 2020). Selinay & Scedil;enkal Turhan was supported by the TUBITAK 2211-C programme. The authors would like to thank Hande Yuece for her help during animal necropsy. The authors would like to thank Taha Bartu Hayal for his help during dot blot analysis. The authors would like to thank Yeditepe University Writing Center and Hakan & Scedil;entuerk for their proofreading support.
dc.identifier.doi10.1002/advs.202407567
dc.identifier.issn2198-3844
dc.identifier.issue43
dc.identifier.orcid0000-0003-4160-2270
dc.identifier.pmid39331961
dc.identifier.scopus2-s2.0-85205261428
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/advs.202407567
dc.identifier.urihttps://hdl.handle.net/11616/110016
dc.identifier.volume11
dc.identifier.wosWOS:001321491200001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofAdvanced Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250329
dc.subject3D culture
dc.subjecthypoparathyroidism
dc.subjectorganoid
dc.subjectparathyroid
dc.subjectparathyroid organoid
dc.subjectpluripotent stem cell
dc.titleInduced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function
dc.typeArticle

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