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

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Milou E. Noltes , Luc Sondorp , Laura Kracht , Inês F. Antunes , René Wardenaar , Wendy Kelder , A Kemper , Wiktor Szymański , Wouter T. Zandee , Liesbeth Jansen , Adrienne H. Brouwers , Robert P. Coppes , Schelto Kruijff ·

YOU? · · 2022 · Open Access · · DOI: https://doi.org/10.1101/2022.03.24.485627

Parathyroid diseases are characterized by dysregulation of calcium homeostasis and alterations in parathyroid hormone (PTH) excretion. The understanding of parathyroid hyperplastic growth and the development of parathyroid-targeted treatment and imaging tracers could benefit from in vitro models. Therefore, we aim to establish stem cell-derived, three-dimensional organoids representing human parathyroid tissue in vitro . Patient-derived hyperplastic parathyroid tissue was dispersed and parathyroid organoids (PTO) were cultured and characterized. PTO-derived cells were shown to exhibit in vitro self-renewal over several passages, indicative of the presence of putative stem cells. Immunofluorescence and RNA-sequencing confirm that PTO phenocopy hyperplastic parathyroid tissue. Exposure of PTO to increasing calcium concentrations and to PTH-lowering drugs resulted in a significantly reduced PTH excretion. Next to this, the PTO showed specific binding of 11 C-methionine to the targeted receptor. Additionally, when organoids were incubated with 99m Tc-sestamibi, we observed a higher uptake in PTOs from patients with a 99m Tc-sestamibi positive scan compared to patients with a negative scan. These data show functionality of PTOs resembling the parathyroid. In conclusion, we present a patient-derived PTO culture, that recapitulates the originating tissue on gene and protein expression and functionality. This PTO model paves the way for future physiology studies and therapeutic target and tracer discovery.

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Parathyroid hormone Organoid In vitro Parathyroid chief cell Calcium-sensing receptor Chemistry Internal medicine Endocrinology Calcium Medicine Biology Cell biology Biochemistry

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2022.03.24.485627
PDF: https://www.biorxiv.org/content/biorxiv/early/2022/03/25/2022.03.24.485627.full.pdf
OA Status: green
Cited By: 2
References: 71
Related Works: 10
OpenAlex ID: https://openalex.org/W4220817195

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OpenAlex ID: https://openalex.org/W4220817195

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DOI: https://doi.org/10.1101/2022.03.24.485627

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

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Type: preprint

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Language: en

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Publication year: 2022

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Publication date: 2022-03-25

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Authors: Milou E. Noltes, Luc Sondorp, Laura Kracht, Inês F. Antunes, René Wardenaar, Wendy Kelder, A Kemper, Wiktor Szymański, Wouter T. Zandee, Liesbeth Jansen, Adrienne H. Brouwers, Robert P. Coppes, Schelto Kruijff

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Landing page: https://doi.org/10.1101/2022.03.24.485627

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PDF URL: https://www.biorxiv.org/content/biorxiv/early/2022/03/25/2022.03.24.485627.full.pdf

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OA URL: https://www.biorxiv.org/content/biorxiv/early/2022/03/25/2022.03.24.485627.full.pdf

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Concepts: Parathyroid hormone, Organoid, In vitro, Parathyroid chief cell, Calcium-sensing receptor, Chemistry, Internal medicine, Endocrinology, Calcium, Medicine, Biology, Cell biology, Biochemistry

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Cited by: 2

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References (count): 71

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