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Patient-derived parathyroid organoids as a tracer and drug-screening application model
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 parathyroi...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669499/ https://www.ncbi.nlm.nih.gov/pubmed/36306782 http://dx.doi.org/10.1016/j.stemcr.2022.09.015 |
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author | Noltes, Milou E. Sondorp, Luc H.J. Kracht, Laura Antunes, Inês F. Wardenaar, René Kelder, Wendy Kemper, Annelies Szymanski, Wiktor Zandee, Wouter T. Jansen, Liesbeth Brouwers, Adrienne H. Coppes, Robert P. Kruijff, Schelto |
author_facet | Noltes, Milou E. Sondorp, Luc H.J. Kracht, Laura Antunes, Inês F. Wardenaar, René Kelder, Wendy Kemper, Annelies Szymanski, Wiktor Zandee, Wouter T. Jansen, Liesbeth Brouwers, Adrienne H. Coppes, Robert P. Kruijff, Schelto |
author_sort | Noltes, Milou E. |
collection | PubMed |
description | 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 (11)C-methionine and (99m)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. |
format | Online Article Text |
id | pubmed-9669499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-96694992022-11-18 Patient-derived parathyroid organoids as a tracer and drug-screening application model Noltes, Milou E. Sondorp, Luc H.J. Kracht, Laura Antunes, Inês F. Wardenaar, René Kelder, Wendy Kemper, Annelies Szymanski, Wiktor Zandee, Wouter T. Jansen, Liesbeth Brouwers, Adrienne H. Coppes, Robert P. Kruijff, Schelto Stem Cell Reports Article 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 (11)C-methionine and (99m)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. Elsevier 2022-10-27 /pmc/articles/PMC9669499/ /pubmed/36306782 http://dx.doi.org/10.1016/j.stemcr.2022.09.015 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Noltes, Milou E. Sondorp, Luc H.J. Kracht, Laura Antunes, Inês F. Wardenaar, René Kelder, Wendy Kemper, Annelies Szymanski, Wiktor Zandee, Wouter T. Jansen, Liesbeth Brouwers, Adrienne H. Coppes, Robert P. Kruijff, Schelto Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title | Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title_full | Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title_fullStr | Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title_full_unstemmed | Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title_short | Patient-derived parathyroid organoids as a tracer and drug-screening application model |
title_sort | patient-derived parathyroid organoids as a tracer and drug-screening application model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669499/ https://www.ncbi.nlm.nih.gov/pubmed/36306782 http://dx.doi.org/10.1016/j.stemcr.2022.09.015 |
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