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

Milou E Noltes; Luc H J Sondorp; Laura Kracht; Inês F Antunes; René Wardenaar; Wendy Kelder; Annelies Kemper; Wiktor Szymanski; Wouter T Zandee; Liesbeth Jansen; Adrienne H Brouwers; Robert P Coppes; Schelto Kruijff

doi:10.1016/j.stemcr.2022.09.015

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

Stem Cell Reports. 2022 Nov 8;17(11):2518-2530. doi: 10.1016/j.stemcr.2022.09.015. Epub 2022 Oct 27.

Authors

Affiliations

¹ Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Department of Ageing Biology/ERIBA, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁶ Department of Surgery, Martini Hospital, Groningen, the Netherlands.
⁷ Department of Surgery, Treant Hospital, Hoogeveen, the Netherlands.
⁸ Stratingh Institute for Chemistry, University of Groningen, Groningen, Groningen, the Netherlands; Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹⁰ Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹¹ Department of Biomedical Sciences of Cells and Systems, Section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: r.p.coppes@umcg.nl.
¹² Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: s.kruijff@umcg.nl.

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: SPECT/PET tracer; drug screening; endocrine diseases; hyperparathyroidism; parathyroid glands; patient-derived organoid model; stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Calcium
Humans
Hyperparathyroidism, Primary*
Organoids*
Parathyroid Glands
Technetium Tc 99m Sestamibi

Substances

Calcium
Technetium Tc 99m Sestamibi