Researchers from Northwestern produced EVATAR, a modular system designed to replicate hormone signaling in the human menstrual cycle. Photo: Northwestern University Feinberg School of Medicine
Researchers have been looking for better ways to study human biology. Cells in a dish don’t capture the body’s complexity and generally don’t live that long. Recent advances in 3D organoids often fall short on their own. But now, researchers at Northwestern University Feinberg School of Medicine have developed a modular system that incorporates all the necessary organ types to replicate hormone signaling in the human menstrual cycle.
Called EVATAR (a combo of avatar and Eve), the system’s various modules contribute 3D models of human fallopian tube, uterus, cervix, liver and mouse ovary tissue. Microfluidics transfer a universal medium that acts like blood and carries hormonal and other signals between tissues. This communal approach produces a better model.
“They were sharing all this media and releasing factors that were propagating each other,” said Julie Kim, research professor and co-author on the team’s Nature Communications paper in a phone interview. “They survived better and responded to hormones better – more so than if they were alone in a static environment. These different cultures together in this microfluidic platform are able to survive for a whole menstrual cycle, 28 days, which is a long time for cells to grow in culture.”
The effort pulled in experts on each tissue type – Kim’s lab focused on the uterus. Draper laboratory helped engineer the various connected boxes. Because we don’t take out healthy human ovaries, researchers used mouse ovaries, but even that was a win.
“The mouse estrus cycle is only four days long,” said Kim. “But by putting it in a dish and stimulating with hormones, like FSH and LH, we got 14 days of estrogen and 14 days of progesterone.”
The research led to a lot of firsts, such as new 3D models for uterus and cervix, but it’s the applications that are generating the team’s excitement. EVATAR could enhance their ability to study many conditions, such as fibroids, endometriosis and endometrial cancer.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
“If we could study tumors long-term in a microfluidic system, then we could see how tumors respond to progestin and see if we can use these types of platforms as mini clinical trials for compounds that can affect these diseases,” said Kim.
The project was spawned by NIH efforts to create a “body-on-a-chip.” The agency solicited proposals for a variety of tissues – cardiovascular, kidney, bowel – though, according to Kim, reproductive tissue was notably absent. The Northwestern team took that as a source of motivation.
“Teresa Woodruff (director of the Women’s Health Research Institute and senior author on the paper) said we need a reproductive tract,” said Kim.
Their work is part of a major push to find better models to study human biology, test drugs for safety and efficacy and ultimately personalize care. Companies like Hµrel, Ascendence Bio and Tissuse have developed organs on chips. Others, like Organovo and BioBots, are creating or enabling 3D tissue printing.
Still, there’s lots more to do. The Northwestern group will be working on a male counterpart to EVATAR and there are other tissues that could improve their female model.
“We have only a couple of cell types in the endometrium,” says Kim. “There are more types that play an important role. If we put in blood vessels, immune cells and other cell types, we could see the tissue differentiate and eventually bleed.”
