Patient-derived Parathyroid Organoids As a Tracer and Drug-screening Application Model

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2022 Oct 28

PMID 36306782

Authors

Milou E Noltes

Luc H J Sondorp

Laura Kracht

Ines F Antunes

Rene Wardenaar

Wendy Kelder

Annelies Kemper

Wiktor Szymanski

Wouter T Zandee

Liesbeth Jansen

Adrienne H Brouwers

Robert P Coppes

Schelto Kruijff

Affiliations

Soon will be listed here.

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 C-methionine and 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.

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