Feb. 9, 2023 — For years, women’s health advocates have argued that far more research is needed on women’s bodies and health. The world’s first-ever “vagina on a chip,” recently developed at Harvard’s Wyss Institute for Biologically Inspired Engineering, could go a long way to making that happen.
“Women’s health has not received the attention it deserves,” says Don Ingber, MD, PhD, who led the team that created the vagina chip. The advance quickly drew media attention after it was reported in the journal Microbiome in late November. But researchers hope for more than headlines. They see the chip as a way to facilitate vaginal health research and open the door to vital new treatments.
By now, you may have heard of “organs on chips”: tiny devices about the size of a flash drive that are designed to mimic the biological activity of human organs. These glass chips contain living human cells within grooves that allow the passage of fluid, to either maintain or disrupt the cells’ function. So far, Ingber and his team at the Wyss Institute have developed more than 15 organ chip models, including chips that mimic the lung, intestine, kidney, and bone marrow.
The idea to develop a vagina chip grew out of research, funded by the Gates Foundation, on a childhood disease called environmental enteric dysfunction, an intestinal disease most commonly found in low-resource nations that is the second leading cause of death in children under 5. That’s when Ingber discovered just how much the child’s microbiome influences this disease.
Stemming from that work, the Gates Foundation turned its attention to newborn health — in particular, the impact of bacterial vaginosis, an imbalance in the vagina’s bacterial makeup. Bacterial vaginosis occurs in 1 out of 4 women worldwide and has been linked to premature birth as well as HIV, HPV persistence, and cervical cancer.
Upon establishing the Vaginal Microbiome Research Consortium, the foundation asked Ingber to engineer an organ chip that mimicked the vagina’s microbiome. The goal was to test “live biotherapeutic products,” or living microbes like probiotics, that might restore the vagina’s microbiome to health.
No other preclinical model exists to perform tests like that, says Ingber.
“The vagina chip is a way to help make some advances,” he says.
Pushing for More Women’s Health Research
The Gates Foundation recognized that women’s reproductive health is a major issue, not only in low-income nations, but everywhere around the world. As the project evolved, Ingber began to hear from female colleagues about how neglected women’s reproductive health is in medical science.
“It is something I became sensitive to and realized this is just the starting point,” Ingber says.
Take bacterial vaginosis, for example. Since 1982, treatment has revolved around the same two antibiotics. That’s partly because there is no animal model to study. No other species has the same vaginal bacterial community as humans do.
That makes developing any new therapy “incredibly challenging,” explains Caroline Mitchell, MD, MPH, an OB/GYN at Massachusetts General Hospital and a member of the consortium.
It turns out, replicating the vagina in a lab dish is, to use the technical term, very hard.
“That’s where a vagina chip offers an opportunity,” Mitchell says. “It’s not super high-throughput, but it’s way more high-throughput than a [human] clinical trial.”
As such, the vagina chip could help scientists find new treatments much faster.
Like Ingber, Mitchell also sees the chip as a way to bring more attention to the largely unmet needs in female reproductive medicine.
“Women’s reproductive health has been under-resourced, under-prioritized, and largely disregarded for decades,” she says. And the time may be ripe for change: Mitchell says she was encouraged by the National Institutes of Health’s Advancing NIH Research on the Health of Women conference, held in 2021 in response to a congressional request to address women’s health research efforts.
Beyond bacterial vaginosis, Mitchell imagines the chip could help scientists find new treatments for vaginal yeast infection (candidiasis), chlamydia, and endometriosis. As with bacterial vaginosis, medicines for vaginal yeast infections have not advanced in decades, Mitchell says. Efforts to develop a vaccine for chlamydia — which can cause permanent damage to a woman’s reproductive system — have dragged on for many years. And endometriosis, an often painful condition in which the tissue that makes up the uterine lining grows outside the uterus, remains under-researched despite affecting 10% of childbearing-age women.
While some mouse models are used in chlamydia research, it’s hard to say if they’ll translate to humans, given the vaginal and cervical bacterial differences.
“Our understanding of the basic physiology of the environment of the vagina and cervix is another area where we’re woefully ignorant,” Mitchell says.
To that end, Ingber’s team is developing more complex chips mimicking the vagina and the cervix. One of his team members wants to use the chips to study infertility. The researchers have already used the chips to see how bacterial vaginosis and mucous changes impact the way sperm migrates up the reproductive tract.
The lab is now linking vagina and cervix chips together to study viral infections of the cervix, like HPV, and all types of bacterial diseases of the vaginal tract. By applying cervical mucus to the vagina chip, they hope to learn more about how female reproductive tissues respond to infection and inflammation.
“I always say that organ chips are like synthetic biology at the cell tissue and organ level,” says Ingber. “You start simple and see if you [can] mimic a clinical situation.”
As they make the chips more complex – perhaps by adding blood vessel cells and female hormones – Ingber foresees being able to study the response to hormonal changes during the menstrual cycle.
“We can begin to explore the effects of cycling over time as well as other types of hormonal effects,” he says.
Ingber also envisions linking the vagina chip to other organ chips – he’s already succeeded in linking eight different organ types together. But for now, the team hopes the vagina chip will enhance our understanding of basic female reproductive biology and speed up the process of developing new treatments for women’s health.