Despite affecting 1 in 10 women during their fertile years, and notwithstanding recent public awareness campaigns, endometriosis may not receive the attention it deserves. Often, symptoms are discounted, and diagnoses missed, in part because of the normalization of menstrual pain. Other endometrial diseases can be neglected. If, for example, endometrial cancer is overlooked during its early stages, opportunities for timely—and effective—interventions may be lost.
To advance the study of endometrial diseases, scientists at KU Leuven have developed endometrial tissue–derived organoids, three-dimensional cell structures that can capture healthy tissue dynamics, represent endometrial pathologies, and display patient-specific drug responses.
Using tissue fragments and cells from clinical biopsies, a KU Leuven team led by Hugo Vankelecom, PhD, professor, grew organoids from a healthy endometrium in 2017. And now the team has gone considerably further, developing organoids from a broad spectrum of endometrial diseases, including endometriosis and endometrial cancer.
The new work was described in a paper (“Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening”) that appeared August 1 in the journal Nature Cell Biology. The paper describes how Vankelecom and colleagues developed multiple organoid models that could provide powerful research models and drug screening and discovery tools.
“Organoids from endometriosis show disease-associated traits and cancer-linked mutations,” the article’s authors wrote. “Endometrial cancer-derived organoids accurately capture cancer subtypes, replicate the mutational landscape of the tumors, 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.”
Diseases of the endometrium are an important cause of infertility. One example is endometriosis, which is characterized by growth of endometrial-like tissue outside the uterine cavity, resulting in chronic abdominal pain and painful sexual intercourse. Up to half of the patients are subfertile or infertile. Treatment usually requires surgery and permanent hormonal therapy, which is incompatible with pregnancy.
Another important disorder is endometrial cancer, the most common gynecological cancer, with tumors growing in and from the endometrium. We need a better understanding of, and more effective treatments for both diseases. But in order to make progress, researchers have to be able to grow and study the endometrium in the lab.
“The organoids form ‘avatars,’ as it were, of the diseased tissue and can also be used to test the effect of drugs and new drug candidates,” Vankelecom explained. “Our study shows that endometrial cancer organoids of different patients are each in a specific way sensitive to chemotherapeutic drugs. Further research will show whether such tests can be of help in the clinical treatment of individual patients. This is an example of what we call personalized medicine.
“We now have a biobank of organoids from endometrium in healthy and diseased conditions. This can help us discover how an aberrantly functioning endometrium causes infertility and then look for treatments. Our new research model offers the potential to better understand and eventually treat uterine diseases such as endometriosis.”
