人类甲状腺微组织模型的表征,用于测试甲状腺破坏性化学物质
E Rogers1, E K Breathwaite1, T Nguyen-Jones1
1Research and Development, LifeSciences Division, LifeNet Health, Va Beach, VA, United States.
Frontiers in toxicology
|August 8, 2024
概括
使用人类甲状腺细胞的新3D微组织模型有效模仿甲状腺激素的产生. 这种基于人类的体外检测系统可以选甲状腺破坏性化学物质,有助于危险的特征.
科学领域:
- 内分泌学和毒理学.
- 在人甲状腺功能的体外建模.
背景情况:
- 甲状腺激素 (T4) 合成中断导致人类发育和认知障碍.
- 现有的体外模型缺乏人类细胞架构和T4生产能力.
- 物种差异需要基于人体的甲状腺破坏性化学物质 (TDC) 查系统.
研究的目的:
- 开发和描述一种基于人体的体外模型,用于T4合成和查TDCs.
- 评估在3D微组织中使用冷保存的原始人体甲状腺细胞的可行性.
- 评估该模型重新总结甲状腺细胞结构和T4生产的能力.
主要方法:
- 在通道一 (p'1) 处冷保存的原始人体甲状腺细胞在Matrigel®上在3D微组织中培养.
- 甲状腺刺激激素 (TSH) 用于刺激甲状腺细胞并诱导卵泡结构的形成.
- 测量了甲状腺蛋白 (TG) 和T4的产生,并评估了原型TPO抑制剂的抑制.
主要成果:
- 甲状腺细胞在4-5天内形成了稳定的3D微组织,具有>80%的EpCAM+细胞.
- 在特定的CD90+细胞比例,种植密度和TSH度下,发生了最佳的TG和T4产生.
- 在微组织模型中确定了TPO抑制剂 (6-propyl-2-thiouracil和methimazole) 的IC50值.
结论:
- 在3D微组织中冷保存的p1人类甲状腺细胞提供了强大的甲状腺功能体外模型.
- 这个模型有效地回顾了甲状腺细胞结构和T4生产.
- 该系统有望优先考虑直接作用于甲状腺的潜在TDC.
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