A miniaturized version of endometrium: organoids for endometriosis research

A promising endometriosis model for drug screening

Key Points

Highlight:

• Endometrial diseases including endometriosis are a major health burden for women.
• However, current research is limited by useful models that can recapitulate the diseases in human.

Importance:

• Development of organoid models that can capture endometrial diseases provides powerful tools to study the conditions and perform large scale drug screening.

What's done here:

• Long-term organoids culture were derived from patients’ endometrium tissues.
• The patient-derived organoid lines include 16 healthy endometria, 9 matched eutopic and ectopic endometrium, 12 ectopic endometria, 13 hyperplastic endometria, and 14 endometrial cancer.
• Phenotypic, genomic and transcriptomic studies were performed on organoids derived to assess whether they recapitulate the clinical disease and suitability as a drug screening platform.

Data:

• Endometriosis organoids showed disease-associated traits and cancer-linked mutations.
• Endometrial cancer organoids replicated the mutational landscape of the tumors and showed drug responses similar to the patients.
• Other organoids involving endometrial hyperplasia and Lynch syndrome were also established and showed in concordance gene mutations.
• The organoids also showed similarities to original lesion when transplanted in vivo.

Limitation:

• While the number of total patient-derived organoid lines were large, the number of disease-specific lines was relatively small, thus study conclusions must be interpreted with caution.

Lay Summary

Organoids are a miniaturized version of a tissue that is produced in culture through three dimensions techniques in order to better mimic the tissues of origin. These cultures are supposed to better replicate the complexity of a biological organ/disease.

Endometrial disorders are a major problem in women’s health and one of the main causes of infertility. Some of the most common conditions include endometriosis and endometrial cancer. However, the pathogenesis of these conditions is not fully understood. In addition, there is a lack of a reliable model to study endometrial diseases.

This research article by Boretto and Vancelecom et al. from Laboratory of Tissue Plasticity in Health and Disease, Stem Cell and Developmental Biology Cluster, Department of Development and Regeneration, Leuven, Belgium have developed three-dimensional in vitro organoids from human endometrium and diseased endometrium to better recapitulate the biology of these tissues.

A large number of patient-derived endometrial organoids were established to recapitulate different endometrial conditions. There were patient-derived organoid lines from 16 healthy endometria, 9 matched eutopic and ectopic endometrium, 12 ectopic endometria, 13 hyperplastic endometria, and 14 endometrial cancer, and recently published in Nature Cell Biology.

The results showed that it was possible to establish long-term organoids of endometriotic lesions, which were also expandable in culture. Because endometriosis is derived from an endometrium-like lesion that grows at ectopic areas such as peritoneum and ovary, the authors have called these culture as "ectopic organoids". Cellular and molecular analyses of the "ectopic organoids" showed that they recapitulate endometriosis disease phenotype in histology and hormone receptor expression.

The transcriptomic RNA and genetic DNA analyses also showed that "ectopic organoids" matches with endometriosis and showed similar cancer-linked mutations.

Furthermore, the authors also established organoid models for endometrial hyperplasia and endometrial cancer, which had recapitulated the mutational and gene expression landscape of the tumor, and maintained features of the primary tissues. Importantly, the organoids can be expanded and transplanted in vivo.

The current study represents an advance in the endometrium research field by improving preclinical study models that can be used for drug screening and other discovery purposes.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/?term=31371824