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功能性甲状腺类器官——基础与转化研究中强大的干细胞衍生模型

Functional Thyroid Organoids-Powerful Stem Cell-Derived Models in Basic and Translational Research.

作者信息

Shankar Meghna Parakkal, Boggian Alessandra, Aparicio-Quiñonez Daniela, Djerbib Sami, Rios-Morris Eduardo, Costagliola Sabine, Romitti Mírian

机构信息

Institute of Jacques-Dumont Interdisciplinary Research in Molecular Human Biology (Jacques-Dumont IRIBHM), Université Libre de Bruxelles, 1070 Brussels, Belgium.

出版信息

Biomolecules. 2025 May 21;15(5):747. doi: 10.3390/biom15050747.

DOI:10.3390/biom15050747
PMID:40427640
Abstract

Thyroid organoids, three-dimensional in vitro models derived from stem cells, have emerged as a powerful tool for studying thyroid development, function, and disease mechanisms. These organoids recapitulate the key aspects of the thyroid gland, including the follicular structure, hormone production, and response to stimuli such as to the thyroid-stimulating hormone (TSH). Recent advances in thyroid organoid technology have established the basis for the modeling of development and thyroid diseases, including congenital hypothyroidism (CH), autoimmune conditions like Graves' disease and Hashimoto's thyroiditis, and other thyroid-related disorders. By utilizing pluripotent stem cells (PSCs) and adult tissue, researchers have generated organoid models suitable for dissecting the mechanisms associated with thyroid development while mimicking the genetic, functional, and inflammatory characteristics of thyroid diseases. Additionally, thyroid organoids offer the potential for personalized medicine by providing a platform to test therapies in a more clinically relevant context. This review highlights the recent progress in thyroid organoid generation, discusses their applications in dissecting the thyroid development mechanisms and disease modeling, and explores their potential for advancing our understanding of the thyroid physiology and pathology. Furthermore, we address the challenges and future directions in the optimization and use of thyroid organoids in translational research.

摘要

甲状腺类器官是源自干细胞的三维体外模型,已成为研究甲状腺发育、功能及疾病机制的有力工具。这些类器官概括了甲状腺的关键特征,包括滤泡结构、激素产生以及对诸如促甲状腺激素(TSH)等刺激的反应。甲状腺类器官技术的最新进展为甲状腺发育及疾病建模奠定了基础,这些疾病包括先天性甲状腺功能减退症(CH)、格雷夫斯病和桥本甲状腺炎等自身免疫性疾病以及其他甲状腺相关病症。通过利用多能干细胞(PSC)和成体组织,研究人员已构建出适用于剖析与甲状腺发育相关机制的类器官模型,同时模拟甲状腺疾病的遗传、功能及炎症特征。此外,甲状腺类器官通过提供一个在更具临床相关性的背景下测试疗法的平台,为个性化医疗带来了潜力。本综述重点介绍了甲状腺类器官生成方面的最新进展,讨论了它们在剖析甲状腺发育机制和疾病建模中的应用,并探讨了它们在增进我们对甲状腺生理学和病理学理解方面的潜力。此外,我们还阐述了在转化研究中优化和使用甲状腺类器官所面临的挑战及未来方向。

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1
Functional Thyroid Organoids-Powerful Stem Cell-Derived Models in Basic and Translational Research.功能性甲状腺类器官——基础与转化研究中强大的干细胞衍生模型
Biomolecules. 2025 May 21;15(5):747. doi: 10.3390/biom15050747.
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本文引用的文献

1
Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells.从诱导多能干细胞中获得可移植的人甲状腺滤泡上皮细胞。
Stem Cell Reports. 2024 Dec 10;19(12):1690-1705. doi: 10.1016/j.stemcr.2024.10.004. Epub 2024 Nov 7.
2
Hypothyroidism due to biallelic variants in IYD: description of 4 families and a novel variant.由于 IYD 中的双等位基因突变导致的甲状腺功能减退症:4 个家族的描述和一个新的变异。
Eur J Endocrinol. 2024 Aug 5;191(2):K5-K9. doi: 10.1093/ejendo/lvae100.
3
Impact of benzo[a]pyrene, PCB153 and sex hormones on human ESC-Derived thyroid follicles using single cell transcriptomics.
利用单细胞转录组学研究苯并[a]芘、PCB153 和性激素对人 ESC 来源甲状腺滤泡的影响。
Environ Int. 2024 Jun;188:108748. doi: 10.1016/j.envint.2024.108748. Epub 2024 May 12.
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State of the Art in 3D Culture Models Applied to Thyroid Cancer.应用于甲状腺癌的3D培养模型的研究现状
Medicina (Kaunas). 2024 Mar 22;60(4):520. doi: 10.3390/medicina60040520.
5
Advances in Thyroid Organoids Research and Applications.甲状腺类器官的研究与应用进展
Endocr Res. 2024 Feb-May;49(2):86-91. doi: 10.1080/07435800.2024.2303632. Epub 2024 Jan 13.
6
Borealin/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures.脑板蛋白/细胞分裂周期蛋白 8 缺乏会改变甲状腺的发育,导致出现乳头状肿瘤样结构。
Front Endocrinol (Lausanne). 2023 Oct 27;14:1286747. doi: 10.3389/fendo.2023.1286747. eCollection 2023.
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Investigation of the effects of phthalates on thyroid models with RNA-Seq and ATAC-Seq.采用 RNA-Seq 和 ATAC-Seq 技术研究邻苯二甲酸酯对甲状腺模型的影响。
Front Endocrinol (Lausanne). 2023 Sep 22;14:1200211. doi: 10.3389/fendo.2023.1200211. eCollection 2023.
8
Progress Toward and Challenges Remaining for Thyroid Tissue Regeneration.甲状腺组织再生的进展和遗留挑战。
Endocrinology. 2023 Aug 28;164(10). doi: 10.1210/endocr/bqad136.
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Organoids: The current status and biomedical applications.类器官:当前现状与生物医学应用
MedComm (2020). 2023 May 17;4(3):e274. doi: 10.1002/mco2.274. eCollection 2023 Jun.
10
Mesodermal FGF and BMP govern the sequential stages of zebrafish thyroid specification.中胚层 FGF 和 BMP 调控斑马鱼甲状腺特化的连续阶段。
Development. 2023 May 15;150(10). doi: 10.1242/dev.201023. Epub 2023 May 16.