干眼病 (DED) 是一个日益严重的公共卫生问题，影响着全世界数百万人，并导致眼部不适和视力障碍。基于动物模型开发治疗药物存在种间差异和人体试验预测不佳的问题。在这里，我们建立了长期 3D 人角膜上皮类器官，它概括了人角膜上皮的细胞谱系和基因表达特征。可以调节类器官在体外进行分化，但添加 FGF10 会抑制这一过程。在高渗诱导的DED类器官模型中，炎症因子的释放增加，导致干细胞的干性受损，功能性粘蛋白1蛋白减少。此外，我们发现类器官可以模拟临床药物治疗反应，这表明角膜上皮类器官是建立离体药物测试平台的有希望的候选者。总之，我们建立了一种功能性、长期 3D 人类上皮类器官，可作为研究功能调节和疾病建模的离体模型。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

Dry eye disease (DED) is a growing public health concern affecting millions of people worldwide and causing ocular discomfort and visual disturbance. Developing its therapeutic drugs based on animal models suffer from interspecies differences and poor prediction of human trials. Here, we established long-term 3D human corneal epithelial organoids, which recapitulated the cell lineages and gene expression signature of the human corneal epithelium. Organoids can be regulated to differentiate ex vivo, but the addition of FGF10 inhibits this process. In the hyperosmolar-induced DED organoid model, the release of inflammatory factors increased, resulting in damage to the stemness of stem cells and a decrease in functional mucin 1 protein. Furthermore, we found that the organoids could mimic clinical drug treatment responses, suggesting that corneal epithelial organoids are promising candidates for establishing a drug testing platform ex vivo. In summary, we established a functional, long-term 3D human epithelial organoid that may serve as an ex vivo model for studying the functional regulation and disease modelling.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.