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Patient-derived parathyroid organoids as a tracer and drug-screening application model.

Authors :
Noltes ME
Sondorp LHJ
Kracht L
Antunes IF
Wardenaar R
Kelder W
Kemper A
Szymanski W
Zandee WT
Jansen L
Brouwers AH
Coppes RP
Kruijff S
Source :
Stem cell reports [Stem Cell Reports] 2022 Nov 08; Vol. 17 (11), pp. 2518-2530. Date of Electronic Publication: 2022 Oct 27.
Publication Year :
2022

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 <superscript>11</superscript> C-methionine and <superscript>99m</superscript> Tc-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.<br />Competing Interests: Conflict of interests The authors declare no competing interests.<br /> (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2213-6711
Volume :
17
Issue :
11
Database :
MEDLINE
Journal :
Stem cell reports
Publication Type :
Academic Journal
Accession number :
36306782
Full Text :
https://doi.org/10.1016/j.stemcr.2022.09.015