Endometriosis is a serious gynaecological disease, that unfortunately is not well understood yet and that cannot be efficiently cured. Researchers hope to discover new medication through organoids: 3D structures of human cells in a Petri dish, made with cells from the patients themselves.
Endometriosis affects one in ten women worldwide during their fertile period. Yet, there is still a big taboo around it. As a result, the disease and its symptoms are still far too little known. The endometrium is the inner lining of the womb. Endometriosis is a disorder in which tissue similar to the endometrial tissue grows outside of the uterine cavity in places where it doesn't belong: on the ovaries and Fallopian tubes, on the peritoneum, the bowels or the rectum.
These adhesions outside of the uterus cause a lot of pain: periods that are so painful that you faint, or that keep you in bed for three days, pain during sexual intercourse, pain at bowel movement or urination, or chronic pain in the lower abdomen and in the pelvis. Unfortunately, endometriosis also often leads to infertility: about thirty to forty percent of women with the disorder experience difficulty getting pregnant or cannot have children at all.
Raising awareness among women and doctors is necessary: patients generally suffer from the disease for seven to ten years before they get diagnosed with endometriosis. Diagnosis is not easy either: only with a laparoscopy - an exploratory surgery - is it possible to detect the damages and adhesions outside the uterus. The treatment usually requires surgery and permanent hormonal therapy, for example with contraception.
The exact cause of endometriosis is not known yet. One possible explanation is that the menstrual cycle initiates the process, says Professor Hugo Vankelecom from the Department of Development and Regeneration, who studies the disease. “Every month, during menstrual periods, the endometrial lining breaks down and is shed. At that moment, endometrium cells may spread through the Fallopian tubes to the wrong places, like the abdominal cavity. However, not every woman develops endometriosis when that happens. Science does not offer a clear explanation yet.”
The menstrual cycle is one of the causes of the pain that patients suffer from: “Monthly, the endometrium is built up and broken down under the influence of hormones. But also the endometrium-like cells outside of the uterus react to those hormones every month, and this causes pain and inflammation. That’s why contraception is often used as a therapy for endometriosis: it keeps the hormonal fluctuations of the menstrual cycle under control. That is however a problem for women who desire to have children. Also, an operation to remove the endometriosis sometimes means that a woman will remain childless.”
Raising awareness among women and doctors is necessary: patients generally suffer from the disease for seven to ten years before they get diagnosed with endometriosis.
3D in the Petri dish
To better understand the disease and to find new treatments, new ways of studying endometriosis are needed. For that purpose, the research group of Vankelecom focuses on organoids: 3D structures of human cells in a Petri dish. “Organoids are also sometimes called mini-organs in 3D, although that is a bit exaggerated. In fact, it involves one compartment of an organ - in this case the epithelial inner lining of the uterus - and not an entire organ.” You start from human cells, obtained through biopsies. If you add the right cocktail of growth factors to the cells in the Petri dish, they grow into a 3D structure. You can partially imitate different organs in this way, depending on where the cells come from. “In this case, the cells come from the endometrium, and organoids are generated to imitate the endometrium.”
Such an organoid opens up a lot of possibilities for research. The first step was to grow organoids from the endometrium tissue of healthy women. That makes it possible to study the menstrual cycle in a Petri dish. If you add or remove hormones - oestrogen and progesterone - the tiny structures imitate the normal reactions of the endometrium, just like during a menstrual cycle.
Healthy and diseased organoids
In a second phase, the researchers created organoids with cells form patients suffering from endometriosis, both from their endometrium as well as from the diseased tissues in the other organs. “We now have a biobank of endometrium organoids in healthy and diseased condition. This can help us to discover how a badly functioning endometrium causes, among other things, infertility.”
The next step is to look for treatments this way. Because you can test a drug candidate on such a ‘diseased’ organoid and examine what the effect is. “It is even possible to have a tailor-made approach for the patient: it is after all a ‘personalised’ organoid”, explains Vankelecom. His research group is going to start testing the drug candidates for endometriosis and there are already companies interested.
It is even possible to have a tailor-made approach for the patient: it is after all a ‘personalised’ organoid.
Thanks to organoids, the testing of new drugs will go much faster in the future, believes Vankelecom. “Now, we do everything by hand: using a pipette, we administer a new candidate drug to the organoids. But that can be automated. Together with the Centre for Drug Design and Discovery (CD3), we are developing a new organoid testing platform: a robotised system would be able to screen thousands of drugs at the same time. This would generate large time and efficiency gains.
And Vankelecom also sees the organoids themselves evolving into mini-organs that are a replica of an entire organ, instead of only a part of it. “We hope that we will soon be able to make assembloids: these are complex organoids consisting of different cell types of the basic organ. That way, they imitate the different compartments of that organ.”
The futuristic terms keep coming, when Vankelecom goes on about his plans for the future. He works together with researchers from Vienna who developed blastoids. To be clear, those are not organoids, but embryo models that are artificially created with stem cells. “If we insert those blastoids in our endometrium organoids, we have an in vitro embryo implantation model. This way, you can simulate and study what happens in the early days of a healthy pregnancy, but also what goes wrong in case of diseases like endometriosis.” This again provides possibilities to search for new medicines for infertility in case of endometriosis or other diseases, but also to discover new ways of contraceptives, for example.
The research with organoids is clearly booming. “Biopsy specimens of endometrium are mostly very small. Until now, it was extremely difficult to use those specimens to grow and multiply tissue in the lab in a reliable manner. The organoids are a huge step forwards in this respect. For disorders that remained under the community’s radar, like endometriosis, that is of the utmost importance. After decades of little scientific progress, the research gets a boost with this. Hopefully, this will soon also translate into therapies that can boost the patients’ quality of life. Although generally considered to be ‘benign’, endometriosis is a very serious disease and certainly deserves more attention.”