Advances in the application of thyroid organoid models in thyroid disease research and clinical translation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Lei , LIU Jiaye ,  LI Zhihui

Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

LI Zhihui, Email: rockoliver@vip.sina.com

Keywords：

thyroid organoid; thyroid cancer; Hashimoto thyroiditis; personalized treatment; clinical translation

DOI：

10.7507/1007-9424.202508084

Video：

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Objective To clarify the application value of thyroid organoids in basic research and clinical translation of thyroid diseases, analyze the key challenges currently faced, and prospect future development directions. Methods Relevant domestic and international literatures in recent years were systematically searched. This review summarized the construction strategies of thyroid organoids, and their application progress in disease model establishment (e.g., thyroid cancer, Hashimoto thyroiditis), drug screening, and personalized treatment. Results Thyroid organoids can highly simulate the morphological structure and gene expression profile of native thyroid tissue. In terms of disease modeling, they can accurately reproduce the pathological characteristics and immune microenvironment of thyroid diseases. In drug screening, organoids can predict the response to radioactive iodine therapy and the sensitivity to targeted drugs, with high consistency between their drug sensitivity results and clinical efficacy. In mechanism research, organoids have been successfully used to reveal the roles of abnormal mitogen-activated protein kinase/phosphatidylinositol 3 kinase-protein kinase B signaling pathways, epithelial-mesenchymal transition, ferroptosis, and immunoregulatory mechanisms in thyroid carcinogenesis and disease progression, providing experimental evidence for target identification. Conclusions As an in vitro model that highly simulates the in vivo environment, thyroid organoids have become an important platform for thyroid disease research. Although challenges remain in standardized construction and clinical translation, with technical optimization and research evidence accumulation, they hold broad prospects in the field of precision medicine.

Citation： CHEN Lei, LIU Jiaye, LI Zhihui. Advances in the application of thyroid organoid models in thyroid disease research and clinical translation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(10): 1269-1274. doi: 10.7507/1007-9424.202508084 Copy

1.	殷德涛, 赵乾. 全球及中国甲状腺癌的发病特征及趋势. 中国普外基础与临床杂志, 2025, 32(6): 687-693.
2.	Vilgelm AE, Bergdorf K, Wolf M, et al. Fine-needle aspiration-based patient-derived cancer organoids. iScience, 2020, 23(8): 101408. doi: 10.1016/j.isci.2020.101408.
3.	Yang H, Chen D. Developing more comprehensive thyroid cancer organoids for precision medicine. Hum Cell, 2024, 37(4): 1229-1230.
4.	Ogundipe VML, Groen AH, Hosper N, et al. Generation and differentiation of adult tissue-derived human thyroid organoids. Stem Cell Reports, 2021, 16(4): 913-925.
5.	Zhang X, Liu J, Ni Y, et al. Modeling clinical radioiodine uptake by using organoids derived from differentiated thyroid cancer. Endocrinology, 2024, 166(1): bqae162. doi: 10.1210/endocr/bqae162.
6.	Xing Z, Cai X, He T, et al. VCP’s nuclear journey: initiated by interacting with KPNB1 to repair DNA damage. Proc Natl Acad Sci U S A, 2025, 122(19): e2416045122. doi: 10.1073/pnas.2416045122.
7.	Yang H, Liang Q, Zhang J, et al. Establishment of papillary thyroid cancer organoid lines from clinical specimens. Front Endocrinol (Lausanne), 2023, 14: 1140888. doi: 10.3389/fendo.2023.1140888.
8.	Scheemaeker S, Inglebert M, Daminet S, et al. Organoids of patient-derived medullary thyroid carcinoma: the first milestone towards a new in vitro model in dogs. Vet Comp Oncol, 2023, 21(1): 111-122.
9.	Undeutsch HJ, Posabella A, Kotton DN, et al. Protocol for directed differentiation of human induced pluripotent stem cells into thyroid follicular epithelial cells. STAR Protoc, 2025, 6(3): 103979. doi: 10.1016/j.xpro.2025.103979.
10.	Liang L, Chen Z, Lei D, et al. APG-115 induces SLC7A11-mediated ferroptosis and upregulates PD-L1 expression in thyroid cancer. ACS Omega, 2025, 10(28): 31099-31107.
11.	Chen D, Tan Y, Li Z, et al. Organoid cultures derived from patients with papillary thyroid cancer. J Clin Endocrinol Metab, 2021, 106(5): 1410-1426.
12.	Xiao H, Liang J, Liu S, et al. Proteomics and organoid culture reveal the underlying pathogenesis of Hashimoto’s thyroiditis. Front Immunol, 2021, 12: 784975. doi: 10.3389/fimmu.2021.784975.
13.	Li G, He L, Huang J, et al. miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis. BMC Med, 2023, 21(1): 206. doi: 10.1186/s12916-023-02914-7.
14.	Pecce V, Sponziello M, Bini S, et al. Establishment and maintenance of thyroid organoids from human cancer cells. STAR Protoc, 2022, 3(2): 101393. doi: 10.1016/j.xpro.2022.101393.
15.	姚金玉, 卢庆苗, 鲁一兵, 等. 甲状腺类器官研究进展. 中华内分泌代谢杂志, 2024, 40(1): 73-76.
16.	Guo Z, Liu J, Zhang X, et al. Precision treatment guided by patient-derived organoids-based drug testing for locally advanced thyroid cancer: a single arm, phase 2 study. Endocrine, 2025, 89(1): 186-196.
17.	Saito Y, Onishi N, Takami H, et al. Development of a functional thyroid model based on an organoid culture system. Biochem Biophys Res Commun, 2018, 497(2): 783-789.
18.	Chen D, Su X, Zhu L, et al. Papillary thyroid cancer organoids harboring BRAFV600E mutation reveal potentially beneficial effects of BRAF inhibitor-based combination therapies. J Transl Med, 2023, 21(1): 9. doi: 10.1186/s12967-022-03848-z.
19.	Lasolle H, Schiavo A, Tourneur A, et al. Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids. Oncogene, 2024, 43(3): 155-170.
20.	Mi L, Liu J, Zhang Y, et al. The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy. Phytomedicine, 2024, 129: 155670. doi: 10.1016/j.phymed.2024.155670.
21.	Ning Q, Liu J, Liu S, et al. TRx0237 induces apoptosis and enhances anti-PD-1 immunotherapeutic efficacy in anaplastic thyroid cancer. Int Immunopharmacol, 2025, 155: 114610. doi: 10.1016/j.intimp.2025.114610.
22.	Jager EC, Sondorp LHJ, Maturi R, et al. Patient-derived medullary thyroid cancer organoids: a potential model for mechanistic studies on diagnostics and therapy. Eur Thyroid J, 2025, 14(5): e240405. doi: 10.1530/ETJ-24-0405.
23.	Meng L, Li H, Fu Y, et al. Somatic DICER1-mutant benign thyroid nodules in adults: a group of follicular nodular disease with continuous growth. J Clin Endocrinol Metab, 2025, 110(6): 1559-1569.
24.	Venegas JA, Onur OE, Kang SC, et al. Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations. Endocr Relat Cancer, 2025, 32(4): e240216. doi: 10.1530/ERC-24-0216.
25.	van der Vaart J, Bosmans L, Sijbesma SF, et al. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism. Proc Natl Acad Sci U S A, 2021, 118(51): e2117017118. doi: 10.1073/pnas.2117017118.
26.	Romitti M, Tourneur A, de Faria da Fonseca B, et al. Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism. Nat Commun, 2022, 13(1): 7057. doi: 10.1038/s41467-022-34776-7.
27.	Sondorp LHJ, Ogundipe VML, Groen AH, et al. Patient-derived papillary thyroid cancer organoids for radioactive iodine refractory screening. Cancers (Basel), 2020, 12(11): 3212. doi: 10.3390/cancers12113212.
28.	Yoo MH, Kim Y, Lee BS. Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: assessment using a human dermal fibroblast-derived extracellular matrix-based thyroid cancer organoid. J Hazard Mater, 2024, 479: 135771. doi: 10.1016/j.jhazmat.2024.135771.
29.	郭子良, 张歆玥, 刘嘉烨, 等. 基于肿瘤类器官指导局部进展期甲状腺乳头状癌临床个性化治疗可行性研究. 中国实用外科杂志, 2023, 43(8): 894-899.
30.	Wang L, Zhang L, Ma R, et al. Semaglutide reprograms macrophages via the GLP-1R/PPARG/ACSL1 pathway to suppress papillary thyroid carcinoma growth. J Clin Endocrinol Metab, 2025, 110(10): 2777-2789.
31.	Tsai S, McOlash L, Palen K, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer, 2018, 18(1): 335. doi: 10.1186/s12885-018-4238-4.
32.	Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 2009, 459(7244): 262-265.
33.	Yi SA, Zhang Y, Rathnam C, et al. Bioengineering approaches for the advanced organoid research. Adv Mater, 2021, 33(45): e2007949. doi: 10.1002/adma.202007949.
34.	Sprangers J, Zaalberg IC, Maurice MM. Organoid-based modeling of intestinal development, regeneration, and repair. Cell Death Differ, 2021, 28(1): 95-107.
35.	Tran T, Song CJ, Nguyen T, et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell Stem Cell, 2022, 29(7): 1083-1101.
36.	Song H, Weinstein HNW, Allegakoen P, et al. Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states. Nat Commun, 2022, 13(1): 141. doi: 10.1038/s41467-021-27322-4.
37.	Deng S, Li C, Cao J, et al. Organ-on-a-chip meets artificial intelligence in drug evaluation. Theranostics, 2023, 13(13): 4526-4558.
38.	Achberger K, Probst C, Haderspeck J, et al. Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. Elife, 2019, 8: e46188. doi: 10.7554/eLife.46188.
39.	Hendriks D, Artegiani B, Hu H, et al. Establishment of human fetal hepatocyte organoids and CRISPR-Cas9-based gene knockin and knockout in organoid cultures from human liver. Nat Protoc, 2021, 16(1): 182-217.

1. 殷德涛, 赵乾. 全球及中国甲状腺癌的发病特征及趋势. 中国普外基础与临床杂志, 2025, 32(6): 687-693.
2. Vilgelm AE, Bergdorf K, Wolf M, et al. Fine-needle aspiration-based patient-derived cancer organoids. iScience, 2020, 23(8): 101408. doi: 10.1016/j.isci.2020.101408.
3. Yang H, Chen D. Developing more comprehensive thyroid cancer organoids for precision medicine. Hum Cell, 2024, 37(4): 1229-1230.
4. Ogundipe VML, Groen AH, Hosper N, et al. Generation and differentiation of adult tissue-derived human thyroid organoids. Stem Cell Reports, 2021, 16(4): 913-925.
5. Zhang X, Liu J, Ni Y, et al. Modeling clinical radioiodine uptake by using organoids derived from differentiated thyroid cancer. Endocrinology, 2024, 166(1): bqae162. doi: 10.1210/endocr/bqae162.
6. Xing Z, Cai X, He T, et al. VCP’s nuclear journey: initiated by interacting with KPNB1 to repair DNA damage. Proc Natl Acad Sci U S A, 2025, 122(19): e2416045122. doi: 10.1073/pnas.2416045122.
7. Yang H, Liang Q, Zhang J, et al. Establishment of papillary thyroid cancer organoid lines from clinical specimens. Front Endocrinol (Lausanne), 2023, 14: 1140888. doi: 10.3389/fendo.2023.1140888.
8. Scheemaeker S, Inglebert M, Daminet S, et al. Organoids of patient-derived medullary thyroid carcinoma: the first milestone towards a new in vitro model in dogs. Vet Comp Oncol, 2023, 21(1): 111-122.
9. Undeutsch HJ, Posabella A, Kotton DN, et al. Protocol for directed differentiation of human induced pluripotent stem cells into thyroid follicular epithelial cells. STAR Protoc, 2025, 6(3): 103979. doi: 10.1016/j.xpro.2025.103979.
10. Liang L, Chen Z, Lei D, et al. APG-115 induces SLC7A11-mediated ferroptosis and upregulates PD-L1 expression in thyroid cancer. ACS Omega, 2025, 10(28): 31099-31107.
11. Chen D, Tan Y, Li Z, et al. Organoid cultures derived from patients with papillary thyroid cancer. J Clin Endocrinol Metab, 2021, 106(5): 1410-1426.
12. Xiao H, Liang J, Liu S, et al. Proteomics and organoid culture reveal the underlying pathogenesis of Hashimoto’s thyroiditis. Front Immunol, 2021, 12: 784975. doi: 10.3389/fimmu.2021.784975.
13. Li G, He L, Huang J, et al. miR-142-3p encapsulated in T lymphocyte-derived tissue small extracellular vesicles induces Treg function defect and thyrocyte destruction in Hashimoto’s thyroiditis. BMC Med, 2023, 21(1): 206. doi: 10.1186/s12916-023-02914-7.
14. Pecce V, Sponziello M, Bini S, et al. Establishment and maintenance of thyroid organoids from human cancer cells. STAR Protoc, 2022, 3(2): 101393. doi: 10.1016/j.xpro.2022.101393.
15. 姚金玉, 卢庆苗, 鲁一兵, 等. 甲状腺类器官研究进展. 中华内分泌代谢杂志, 2024, 40(1): 73-76.
16. Guo Z, Liu J, Zhang X, et al. Precision treatment guided by patient-derived organoids-based drug testing for locally advanced thyroid cancer: a single arm, phase 2 study. Endocrine, 2025, 89(1): 186-196.
17. Saito Y, Onishi N, Takami H, et al. Development of a functional thyroid model based on an organoid culture system. Biochem Biophys Res Commun, 2018, 497(2): 783-789.
18. Chen D, Su X, Zhu L, et al. Papillary thyroid cancer organoids harboring BRAFV600E mutation reveal potentially beneficial effects of BRAF inhibitor-based combination therapies. J Transl Med, 2023, 21(1): 9. doi: 10.1186/s12967-022-03848-z.
19. Lasolle H, Schiavo A, Tourneur A, et al. Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids. Oncogene, 2024, 43(3): 155-170.
20. Mi L, Liu J, Zhang Y, et al. The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy. Phytomedicine, 2024, 129: 155670. doi: 10.1016/j.phymed.2024.155670.
21. Ning Q, Liu J, Liu S, et al. TRx0237 induces apoptosis and enhances anti-PD-1 immunotherapeutic efficacy in anaplastic thyroid cancer. Int Immunopharmacol, 2025, 155: 114610. doi: 10.1016/j.intimp.2025.114610.
22. Jager EC, Sondorp LHJ, Maturi R, et al. Patient-derived medullary thyroid cancer organoids: a potential model for mechanistic studies on diagnostics and therapy. Eur Thyroid J, 2025, 14(5): e240405. doi: 10.1530/ETJ-24-0405.
23. Meng L, Li H, Fu Y, et al. Somatic DICER1-mutant benign thyroid nodules in adults: a group of follicular nodular disease with continuous growth. J Clin Endocrinol Metab, 2025, 110(6): 1559-1569.
24. Venegas JA, Onur OE, Kang SC, et al. Divergent PTEN-p53 interaction upon DNA damage in a human thyroid organoid model with germline PTEN mutations. Endocr Relat Cancer, 2025, 32(4): e240216. doi: 10.1530/ERC-24-0216.
25. van der Vaart J, Bosmans L, Sijbesma SF, et al. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism. Proc Natl Acad Sci U S A, 2021, 118(51): e2117017118. doi: 10.1073/pnas.2117017118.
26. Romitti M, Tourneur A, de Faria da Fonseca B, et al. Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism. Nat Commun, 2022, 13(1): 7057. doi: 10.1038/s41467-022-34776-7.
27. Sondorp LHJ, Ogundipe VML, Groen AH, et al. Patient-derived papillary thyroid cancer organoids for radioactive iodine refractory screening. Cancers (Basel), 2020, 12(11): 3212. doi: 10.3390/cancers12113212.
28. Yoo MH, Kim Y, Lee BS. Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: assessment using a human dermal fibroblast-derived extracellular matrix-based thyroid cancer organoid. J Hazard Mater, 2024, 479: 135771. doi: 10.1016/j.jhazmat.2024.135771.
29. 郭子良, 张歆玥, 刘嘉烨, 等. 基于肿瘤类器官指导局部进展期甲状腺乳头状癌临床个性化治疗可行性研究. 中国实用外科杂志, 2023, 43(8): 894-899.
30. Wang L, Zhang L, Ma R, et al. Semaglutide reprograms macrophages via the GLP-1R/PPARG/ACSL1 pathway to suppress papillary thyroid carcinoma growth. J Clin Endocrinol Metab, 2025, 110(10): 2777-2789.
31. Tsai S, McOlash L, Palen K, et al. Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer, 2018, 18(1): 335. doi: 10.1186/s12885-018-4238-4.
32. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 2009, 459(7244): 262-265.
33. Yi SA, Zhang Y, Rathnam C, et al. Bioengineering approaches for the advanced organoid research. Adv Mater, 2021, 33(45): e2007949. doi: 10.1002/adma.202007949.
34. Sprangers J, Zaalberg IC, Maurice MM. Organoid-based modeling of intestinal development, regeneration, and repair. Cell Death Differ, 2021, 28(1): 95-107.
35. Tran T, Song CJ, Nguyen T, et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell Stem Cell, 2022, 29(7): 1083-1101.
36. Song H, Weinstein HNW, Allegakoen P, et al. Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states. Nat Commun, 2022, 13(1): 141. doi: 10.1038/s41467-021-27322-4.
37. Deng S, Li C, Cao J, et al. Organ-on-a-chip meets artificial intelligence in drug evaluation. Theranostics, 2023, 13(13): 4526-4558.
38. Achberger K, Probst C, Haderspeck J, et al. Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. Elife, 2019, 8: e46188. doi: 10.7554/eLife.46188.
39. Hendriks D, Artegiani B, Hu H, et al. Establishment of human fetal hepatocyte organoids and CRISPR-Cas9-based gene knockin and knockout in organoid cultures from human liver. Nat Protoc, 2021, 16(1): 182-217.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Advances in the application of thyroid organoid models in thyroid disease research and clinical translation

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