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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods
  • Drug Evaluation, Preclinical* / methods
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Endometrium / pathology
  • Female
  • Humans
  • Organoids / drug effects
  • Organoids / metabolism
  • Organoids / pathology*
  • Uterine Diseases / drug therapy
  • Uterine Diseases / metabolism
  • Uterine Diseases / pathology*