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子宫内膜疾病衍生的类器官可捕获临床异质性并适用于药物筛选。

Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening.

机构信息

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.

出版信息

Nat Cell Biol. 2019 Aug;21(8):1041-1051. doi: 10.1038/s41556-019-0360-z. Epub 2019 Aug 1.


DOI:10.1038/s41556-019-0360-z
PMID:31371824
Abstract

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.

摘要

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。

相似文献

[1]
Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening.

Nat Cell Biol. 2019-8-1

[2]
Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors.

Gynecol Oncol. 2019-5-14

[3]
Endometrial Organoids: A New Model for the Research of Endometrial-Related Diseases†.

Biol Reprod. 2020-10-29

[4]
Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome.

J Clin Endocrinol Metab. 2020-3-1

[5]
Establishing patient-derived organoids from human endometrial cancer and normal endometrium.

Front Endocrinol (Lausanne). 2023

[6]
Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

Nat Cell Biol. 2017-5

[7]
Optimization of endometrial cancer organoids establishment by cancer-associated fibroblasts.

Neoplasma. 2022-7

[8]
Patient-derived explants, xenografts and organoids: 3-dimensional patient-relevant pre-clinical models in endometrial cancer.

Gynecol Oncol. 2019-11-22

[9]
Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability.

Development. 2017-5-15

[10]
Endometrial Organoids: A Rising Star for Research on Endometrial Development and Associated Diseases.

Reprod Sci. 2021-6

引用本文的文献

[1]
Decoding adenomyosis pathogenesis using an assembloid model.

Sci China Life Sci. 2025-8-28

[2]
Derivation, expansion and cryopreservation of primary fetal organoids from second and third trimester human amniotic fluid cells.

Nat Protoc. 2025-8-14

[3]
Female Reproductive Tract Organoids: Applications from Physiology to Pathology.

Biomolecules. 2025-6-24

[4]
WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Organoids): endometrial organoids as an emerging technology for endometriosis research.

Mol Hum Reprod. 2025-7-3

[5]
Organoids as powerful models of endometrium epithelium in transcriptomic, cellular and functional mimicry.

Cell Mol Life Sci. 2025-7-7

[6]
Rational design matrix materials for organoid development and application in biomedicine.

Regen Biomater. 2025-5-14

[7]
Integration of Bioengineered Tools in Assisted Reproductive Technologies.

Adv Healthc Mater. 2025-8

[8]
PCOS endometrium-derived epithelial organoids as a novel model to study endometrial dysfunction.

Hum Reprod. 2025-8-1

[9]
Endometrial Organoids and Their Role in Modeling Human Infertility.

Cells. 2025-6-3

[10]
On-chip 3D potency assay for prediction of clinical outcomes for cell therapy candidates for osteoarthritis.

Nat Commun. 2025-5-27

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