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.
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.
Stem Cell Reports. 2022 Nov 8;17(11):2518-2530. doi: 10.1016/j.stemcr.2022.09.015. Epub 2022 Oct 27.
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.
甲状旁腺疾病的特征是钙稳态失调和甲状旁腺激素 (PTH) 排泄改变。甲状旁腺靶向治疗和成像示踪剂的发展可能受益于体外模型。因此，我们旨在建立一个代表人类甲状旁腺组织的患者来源的甲状旁腺类器官模型。增生性甲状旁腺组织被分散，并培养和表征甲状旁腺类器官 (PTO)。PTO 衍生细胞在几个传代中表现出自我更新，表明存在潜在的干细胞。免疫荧光和 RNA 测序证实 PTO 模拟增生性甲状旁腺组织。将 PTO 暴露于增加的钙浓度和降低 PTH 的药物中，导致 PTH 排泄明显减少。PTO 显示出成像示踪剂 C-蛋氨酸和 Tc- sestamibi 的特异性结合。这些数据显示了类似于甲状旁腺的 PTO 的功能。该 PTO 模型在基因和蛋白质表达和功能上再现了起源组织，为未来的生理学研究以及治疗靶点和示踪剂发现铺平了道路。
