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骨髓间充质干细胞在碘诱导的自身免疫性甲状腺炎治疗中的潜力。

Potential of bone marrow mesenchymal stem cells in iodine-induced autoimmune thyroiditis therapy.

作者信息

Liu Xun, Cui Likun, Dong Jianwei, Ren Jiancong, Xu Dongdong, Han Yanshuo, Zhang Jian

出版信息

Eur Thyroid J. 2025 Jun 12;14(3). doi: 10.1530/ETJ-24-0137. Print 2025 Jun 1.

DOI:10.1530/ETJ-24-0137
PMID:40435196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12164285/
Abstract

OBJECTIVE

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease without a cure. Mesenchymal stem cells (MSCs) may offer the opportunity to improve autoimmune thyroiditis.

METHODS

We replicated the pathogenic factors of HT and established a stable autoimmune thyroiditis model in NOD.H-2h4 mice by administering iodine for 12 weeks. We used orthotopic injection to transplant bone MSCs (BMSCs) into the thyroid. Immunohistochemistry, enzyme-linked immunosorbent assay, flow cytometry, and hematoxylin and eosin and immunofluorescence staining were used to evaluate the effects of cell transplantation.

RESULTS

Orthotopic BMSC transplantation decreased serum thyroglobulin antibody and caspase 3 levels; increased proliferating cell nuclear antigen levels; decreased CD4+/CD3+ T cells, Th1/Th2, and Th17/Treg ratios; decreased TNF-alpha (a proinflammatory cytokine) and interferon-gamma levels; and increased transforming growth factor-beta and interleukin-10 levels. In addition, it increased CD90/S100A4 and CD90/TTF-1 co-expression.

CONCLUSION

Orthotopic BMSC transplantation improved the inflammatory environment by regulating the secretion of anti-inflammatory cytokines, promoting regeneration, and reducing apoptosis in the thyroid tissue. Bone marrow-derived stem cells inhibited T cell activation, maintained a balance between T cell subpopulation ratios, and halted thyroiditis progression. Finally, transplanted BMSCs could transform into fibroblasts and thyroid cells. This study elucidated the pathogenesis of HT and provided evidence supporting the potential of MSCs in HT treatments.

摘要

目的

桥本甲状腺炎（HT）是一种常见的自身免疫性疾病，尚无治愈方法。间充质干细胞（MSCs）可能为改善自身免疫性甲状腺炎提供机会。

方法

我们复制了HT的致病因素，并通过给予碘12周，在NOD.H-2h4小鼠中建立了稳定的自身免疫性甲状腺炎模型。我们采用原位注射将骨髓间充质干细胞（BMSCs）移植到甲状腺中。使用免疫组织化学、酶联免疫吸附测定、流式细胞术以及苏木精-伊红和免疫荧光染色来评估细胞移植的效果。

结果

原位BMSC移植降低了血清甲状腺球蛋白抗体和半胱天冬酶3水平；增加了增殖细胞核抗原水平；降低了CD4+/CD3+ T细胞、Th1/Th2和Th17/Treg比值；降低了肿瘤坏死因子-α（一种促炎细胞因子）和干扰素-γ水平；增加了转化生长因子-β和白细胞介素-10水平。此外，它增加了CD90/S100A4和CD90/TTF-1共表达。

结论

原位BMSC移植通过调节抗炎细胞因子的分泌、促进再生以及减少甲状腺组织中的细胞凋亡来改善炎症环境。骨髓来源的干细胞抑制T细胞活化，维持T细胞亚群比例之间的平衡，并阻止甲状腺炎进展。最后，移植的BMSCs可以转化为成纤维细胞和甲状腺细胞。本研究阐明了HT的发病机制，并为MSCs在HT治疗中的潜力提供了支持证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/ffe3a04f692c/ETJ-24-0137fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/a832edecfd54/ETJ-24-0137fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/640e8cbd0da2/ETJ-24-0137fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/763dea5afe92/ETJ-24-0137fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/ffe3a04f692c/ETJ-24-0137fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/a832edecfd54/ETJ-24-0137fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/8155b641ca3d/ETJ-24-0137fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/97d3654fd385/ETJ-24-0137fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/eadfb436250a/ETJ-24-0137fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/7e41343e0821/ETJ-24-0137fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/640e8cbd0da2/ETJ-24-0137fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/763dea5afe92/ETJ-24-0137fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9399/12164285/ffe3a04f692c/ETJ-24-0137fig8.jpg

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