Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Nat Cell Biol. 2019 Aug;21(8):1041-1051. doi: 10.1038/s41556-019-0360-z. Epub 2019 Aug 1.
Endometrial disorders represent a major gynaecological burden. Current research models fail to recapitulate the nature and heterogeneity of these diseases, thereby hampering scientific and clinical progress. Here we developed long-term expandable organoids from a broad spectrum of endometrial pathologies. Organoids from endometriosis show disease-associated traits and cancer-linked mutations. Endometrial cancer-derived organoids accurately capture cancer subtypes, replicate the mutational landscape of the tumours and display patient-specific drug responses. Organoids were also established from precancerous pathologies encompassing endometrial hyperplasia and Lynch syndrome, and inherited gene mutations were maintained. Endometrial disease organoids reproduced the original lesion when transplanted in vivo. In summary, we developed multiple organoid models that capture endometrial disease diversity and will provide powerful research models and drug screening and discovery tools.
子宫内膜疾病是妇科的主要负担。目前的研究模型无法重现这些疾病的性质和异质性,从而阻碍了科学和临床的进展。在这里,我们从广泛的子宫内膜病变中开发了可长期扩增的类器官。来自子宫内膜异位症的类器官显示出与疾病相关的特征和与癌症相关的突变。源自子宫内膜癌的类器官准确地捕获了癌症亚型,复制了肿瘤的突变景观,并显示出患者特异性的药物反应。还从包括子宫内膜增生和林奇综合征在内的癌前病变以及遗传基因突变中建立了类器官,并且这些基因突变得以维持。将子宫内膜疾病类器官移植到体内后可重现原始病变。总之,我们开发了多种能够捕捉子宫内膜疾病多样性的类器官模型,这些模型将为研究提供强大的模型以及药物筛选和发现工具。
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