Organ on a chip: a 3D model for studying endometriosis
The MIT Center for Gynepathology Research (CGR) launched in 2009 seeking to improve current understanding of conditions that predominantly affect women, often focused on reproductive health. The Center, co-led by scientific director Linda Griffith, PhD, of the MIT Bioengineering department, and Keith Isaacson, MD, of Harvard Medical School, is unique in its approach because researchers apply tools from bioengineering, such as tissue engineering, to study a topic previously confined to traditional methods of biological analysis.
For example, to improve understanding of the ways hormones impact the tissue that lines the uterus, bioengineering PhD student Christi Cook has created a 3D tissue culturing system that supports distinct layers of different cell types, sourced from endometrial biopsies, that can be exposed to hormones such as estrogen and progesterone, in a way that mimics the month-long menstrual cycle. “My goal has been to develop better in vitro model systems so that we can understand some of the endometrial pathologies that women face,” Cook said. “It’s taken a couple years to develop the model system, and we’re now beginning to understand and use them to study things like inflammation and how that impacts hormone responsiveness.”
Many gynepathological conditions are characterized by changes in the uterine cells’ hormone responsiveness, including adenomyosis, infertility, leiomyoma, and endometriosis. Endometriosis, a primary focus of CGR, affects about 10% of women and occurs when cells similar to the endometrium, the innermost lining of the uterus, grow elsewhere in the body, usually around the pelvic and abdominal areas. Not all women with this condition show symptoms, but those who do can experience debilitating chronic pain.
Currently, treatments for endometriosis begin with a first line treatment of oral contraceptives, but not every patient can tolerate them and they aren’t effective for every patient. If oral contraceptives are ineffective or aren’t an option, the next step would be hormone antagonists, which block cells’ ability to sense hormones. “These can have nasty side effects — it’s like a fake menopause, so this isn’t ideal,” Cook said. Another option for endometriosis patients is surgery to remove the misplaced endometrial cells that characterize endometriosis, but that is also not entirely effective. “There’s no perfect way to treat this disease right now, what works for someone might not work for someone else and we still don’t know why,” Cook said.
CGR also has a number of collaborations around MIT, including running an IAP class on endometriosis and working with the MIT iGEM team in 2016 as they created a synthetic biology tool for diagnosing endometriosis. “[Linda Griffith] is definitely excited to talk to any researcher on campus who has a potential interest in seeing what sorts of unique projects and ideas can come out of pairing together unusual departments,” Cook said.
One such collaboration is between CGR and CSAIL to develop an app that could be launched in Isaacson’s clinic so patients can track the day-to-day impact of their disease, endometriosis or otherwise. CGR would then collect and analyze this data, comparing it to the patient biopsies they have in the lab. Currently, endometriosis is classified based on the size of the misplaced cellular growths, but the severity of a patient’s symptoms don’t necessarily match the apparent severity of the disease stage. “Maybe there’s different types of endometriosis, but right now we’re lumping it as one single disease,” Cook suggested. If there turn out to be subsets of day-to-day symptoms of endometriosis, this could lead research into new classifications of endometriosis.