@article{35d67ed40c9741cd82ebcfa219a135fd,
title = "Patient-derived parathyroid organoids as a tracer and drug-screening application model",
abstract = "Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish a patient-derived parathyroid organoid model representing human parathyroid tissue. Hyperplastic parathyroid tissue was dispersed, and parathyroid organoids (PTOs) were cultured and characterized. PTO-derived cells exhibited self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA sequencing confirmed that PTOs phenocopy hyperplastic parathyroid tissue. Exposure of PTOs to increasing calcium concentrations and PTH-lowering drugs resulted in significantly reduced PTH excretion. PTOs showed specific binding of the imaging tracers 11C-methionine and 99mTc-sestamibi. These data show the functionality of PTOs resembling the parathyroid. This PTO model recapitulates the originating tissue on gene and protein expression and functionality, paving the way for future physiology studies and therapeutic target and tracer discovery.",
keywords = "drug screening, endocrine diseases, hyperparathyroidism, parathyroid glands, patient-derived organoid model, SPECT/PET tracer, stem cells",
author = "Noltes, {Milou E.} and Sondorp, {Luc H.J.} and Laura Kracht and Antunes, {In{\^e}s F.} and Ren{\'e} Wardenaar and Wendy Kelder and Annelies Kemper and Wiktor Szymanski and Zandee, {Wouter T.} and Liesbeth Jansen and Brouwers, {Adrienne H.} and Coppes, {Robert P.} and Schelto Kruijff",
note = "Funding Information: We thank the surgeons and pathology departments of the University Medical Center Groningen, Treant location Bethesda, and the Martini Hospital for collecting and distributing hyperplastic parathyroid gland tissue. Sequencing was performed with excellent assistance from Diana Spierings and the ERIBA Research Sequencing Facility. Part of the work was performed at the UMCG Imaging and Microscopy Center (UMIC). This work was partly funded by UMCG Cancer Research Fund 490178 (to R.P.C. and S.K.). The authors declare no competing interests. Funding Information: We thank the surgeons and pathology departments of the University Medical Center Groningen, Treant location Bethesda, and the Martini Hospital for collecting and distributing hyperplastic parathyroid gland tissue. Sequencing was performed with excellent assistance from Diana Spierings and the ERIBA Research Sequencing Facility. Part of the work was performed at the UMCG Imaging and Microscopy Center (UMIC). This work was partly funded by UMCG Cancer Research Fund 490178 (to R.P.C. and S.K.). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = nov,
day = "8",
doi = "10.1016/j.stemcr.2022.09.015",
language = "English",
volume = "17",
pages = "2518--2530",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "CELL PRESS",
number = "11",
}