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

Matteo Boretto, Nina Maenhoudt, Xinlong Luo, Aurélie Hennes, Bram Boeckx, Bich Bui, Ruben Heremans, Lisa Perneel, Hiroto Kobayashi, Indra Van Zundert, Hilde Brems, Benoit Cox, Marc Ferrante, Hiroshi Uji-I, Kian Peng Koh, Thomas D’Hooghe, Arne Vanhie, Ignace Vergote, Christel Meuleman, Carla Tomassetti, Diether Lambrechts, Joris Vriens, Dirk Timmerman, Hugo Vankelecom (see publication in Journal )


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.