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

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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.

Original languageEnglish
Pages (from-to)2518-2530
Number of pages13
JournalStem Cell Reports
Volume17
Issue number11
DOIs
Publication statusPublished - 8-Nov-2022

Keywords

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

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