Dr. Don Ingber makes organs for a living. Using flexible pieces of silicone sculpted into tiny channels, he grows tissue that can mimic the complex physical interactions between cells and fluids, creating malleable three-dimensional organ models.
Over the past decade, Harvard bioengineer Dr. Ingber has made more than 15 of these organ chips, including those simulating the lungs, liver, intestines and skin. And now, as described in an article published last month, he’s added a much less studied organ to the list: the vagina.
The “vagina on chip” was made from vaginal cells donated by two women. The model was grown inside stick-sized chips of silicone rubber, forming channels that react to fluctuations in estrogen levels and bacteria. The chip successfully mimicked key features of the vaginal microbiome, the teeming communities of bacteria that play a crucial role in the health of the organ, according to the study.
The chip is more realistic than other lab models of the organ, Dr. Ingber said: “It walks, talks, quacks like a human vagina.”
He and other researchers are optimistic the tool could offer a better way to test treatments for bacterial vaginosis, an infection of harmful microbes in the vagina that affects around 30% of women each year.
“It’s a great development, this system,” said Dr. Ahinoam Lev-Sagie, a gynecologist at Hadassah Medical Center in Jerusalem who studies the vaginal microbiome and was not involved in the new study. Safety concerns make it difficult for researchers like her to test new treatments for patients with recurring infections, she said.
It’s not hard to find women willing to give vaginal samples, she said. “But when you want to explore what drugs might work, it’s very, very difficult to find women who are willing to take part in these studies.”
The study, which was funded by the Gates Foundation, used the vaginal chip to mimic how a real vagina responds to good and bad bacterial environments. The researchers showed that the tissue inside the chip reacted positively to a cocktail of lactobacilli, a type of bacteria that digest sugars and produce lactic acid, creating an acidic environment inside the human vagina that protects it from infections. When a different type of bacteria, associated with vaginal infections, was cultured on the chip without lactobacilli present, the inflammation increased and the cells were rapidly damaged.
This reaction is similar to what happens when a person contracts bacterial vaginosis, a condition in which harmful bacteria invade the vaginal microbiome, lowering its acidity and sometimes causing itching and increased discharge.
Bacterial vaginosis is usually treated with antibiotics, but relapse rates are high. When left untreated, bacterial vaginosis increases the risk of sexually transmitted infections and cervical cancer. In pregnant women, it can increase the risk of premature birth or low birth weight.
Despite these risks, bacterial vaginosis—and the vagina itself—remains understudied.
“We don’t really understand how these processes are triggered by bacteria in the vagina or often even which bacteria are responsible,” said Amanda Lewis, a professor at the University of California, San Diego who studies the vaginal microbiome. “As you can imagine, such a crude understanding of such an important physiological system leads to crude interventions, if any at all.”
In 2019, Dr. Lev-Sagie and other researchers in Israel published the results of the world’s first vaginal microbiome transplants. They transferred bacteria-rich secretions from donors with healthy vaginas into the vaginas of five women who had battled recurrent bacterial vaginosis. Screening samples to ensure they were safe and finding patients who were willing to participate was extremely difficult and took many years.
Other models, in animals or in the laboratory, are not effective environments for testing the vaginal microbiome. While the vaginas of healthy humans are composed of approximately 70% lactobacilli, in other mammals lactobacilli rarely make up more than 1% of the vaginal microbiome. And when vaginal cells are mixed with bacteria in a flat Petri dish, the bacteria quickly take over and kill the cells.
Similar drawbacks hamper the development of many drugs, which is why organ chips hold so much promise, said Dr. Ingber, who holds a patent for the design of the silicone chip and founded a company that manufactures them and test them.
“There has been a search for better in vitro models that really mimic the physiological complexity, the structural complexity of tissues,” he said. “And that’s what we did with the organ chips.”
In another paper published this week, Dr. Ingber’s group showed that a liver organ chip was seven to eight times better at predicting human responses to 27 drugs than animal models.
But the vaginal chip has limitations, the scientists said.
Dr. Lev-Sagie of Hadassah Medical Center in Jerusalem noted that the vaginal microbiome changes dramatically in response to menstruation, sexual intercourse, hormonal fluctuations and antibiotic use. And other important types of cells in the vagina, such as immune cells, were not included in the study.
“Real life is much more complicated than the vagina on a chip,” Dr. Lev-Sagie said.
Having a more sophisticated model will require more studies into exactly how the vaginal microbiome works and how it responds to disease, she added. Unlike gut microbiome research, which has advanced rapidly over the past decade, vaginal microbiome work suffers from a lack of funding.
“In the vagina, bacteria were known to be crucial more than a hundred years ago“, says Dr. Lev-Sagie. “We have been doing research for many years, but we are still lagging behind.”
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