Most scientists don’t get to work in a field of their own creation. But Teresa Woodruff is not most scientists. The Northwestern University reproductive biologist coined the term “oncofertility” over a decade ago, when she began helping young cancer patients preserve their ability to become biological parents even after chemotherapy and radiation. Back then, there weren’t any good models to study the female reproductive system, let alone how it responded to drugs. So Woodruff had to create one of those too, though it took nearly five years and two dozen collaborators to pull it off. Today, her team announced a miniature female reproductive tract made of human and mouse tissues that secretes a 28-day cycle of hormones just like the real thing—except it fits in the palm of your hand.
Called Evatar, the model doesn’t look anything like the anatomy textbook illustrations you may have studied in high school health. Instead, a blue liquid runs between its cube- and diamond-shaped clear plastic wells, which are screwed onto a plate and connected to a computer. The first well holds a mini-ovary, the second a mini-fallopian tube, then a mini-uterus, a mini-cervix, and finally a mini-liver. The computer controls the flow between the organs, and members of Woodruff’s lab remove samples to measure hormones like estrogen and progesterone, which ready a woman’s body for pregnancy each month. “This is the first time we’ve been able to model the entire reproductive hormone profile,” says Woodruff. “You might be able to look at two of these tissues together in culture, but five together for a month is almost unheard of.”
Evatar is one of a growing number of organs-on-a-chip systems designed to improve drug screening, though it’s the first to model a menstrual cycle (minus the blood). In the last five years, the US government has spent over $100 million on the technology, with large grants from Darpa and the NIH going to people like Woodruff to help develop prototypes and fill knowledge gaps—of which there are many where the uterus is concerned.
For obvious ethical reasons, pregnant women aren’t allowed to participate in studies of new drugs, and pharmaceutical companies haven’t made a huge effort to test out new candidates in cells or animals of both sexes. So there’s a lot scientists don’t know about how a woman’s body, especially her endocrine system, interacts with drugs. That might help explain why there are still no good treatments for common ailments like endometriosis, fibroids, and cervical, uterine, and ovarian cancers, which together affect as much as 15 percent of American women.
The female reproductive tract, to be fair, is complicated, and so is the new model. “To do something like that you really have to have an expert for each individual part of it,” says Ali Khademhosseini, a tissue engineer at Harvard and MIT who most recently combined a mini-heart and mini-tumor on a chip. “You can’t just buy cells off the shelf and make it work.” So assemble a team of experts is exactly what Woodruff did: Fellow Northwestern researchers Julie Kim and Spiro Getsios developed the uterus and cervix, respectively; Joanna Burdette of the University of Illinois Chicago made the fallopian tubes; and Woodruff herself developed the ovaries. The liver, which was included for its role in metabolizing drugs, was the only off-the-shelf component. While Woodruff used mouse tissue for her ovaries, the other researchers developed their mini-organs from tissues donated by women undergoing surgery for gynecological issues.
Woodruff’s team spent two years getting the tissues to grow on their own before they began combining them with a microfluidics system developed by Charles Stark Draper Laboratory in Cambridge, Massachusetts. The platform works kind of like a Lego board with different bricks you can snap in. It can hold well plates for up to 12 different mini-organs, though so far the most anyone has actually succeeded with is 10—an array of liver-lung interactions. Jeffrey Borenstein, one of the lab’s chief biomedical engineers, said they had to make a few small mechanical tweaks to make it work as a menstrual cycle model, but that the really hard work all happened in Woodruff’s lab. “It’s agnostic to the biology you place on each cube, but it’s not quite as easy as hooking five things up and letting them talk to each other,” he said. “You’ve got to have one blood substitute that supports all the tissues simultaneously. That’s the secret sauce.” Draper has already been approached by a few pharmaceutical companies, including AstraZeneca, about using the technology for drug testing.
Which has Woodruff’s team already looking ahead to the next thing: combining their menstrual model with other micro-organs, like the pancreas and heart, to see how drugs might affect them with an overlay of these hormones, which in real life are always in the background. “We’ve been losing out on the complexity of human physiology,” says Woodruff. “We think this will radically change the way we study a lot of human systems, not just the female reproductive tract.” For now though, finally having a way to study the organs responsible for growing a human life is a pretty good start.