“Vagina on a chip” mimics an organ’s biome so scientists can test drugs against bacterial infections

Scientists have mimicked the intricate biome inside a vagina to help test drugs for bacterial infections that plague 30 percent of women worldwide.

The innovation – a “vagina on a chip” – involves donated vaginal cells that have been matured in silicon chips to form channels that can be used to understand microbiome-tissue interactions.

Developing therapeutics for bacterial vaginosis (BV), a condition in which there are too many bacteria in the vagina, is difficult because the human vaginal microbiome differs from that of other mammals.

The new vagina on a chip is being touted as a solution because the team at Harvard University’s Wyss Institute claims it replicates the microenvironment of human vaginal tissue, including its microbiome in vitro.

Scientists collected vaginal cells from two female volunteers and placed them on silicon chips. Within five days, the cells had matured into different cell layers that corresponded to those in human vaginal tissue.

Gautam Mahajan, Ph.D., a former Wyss Institute researcher and lead author of the study, said in a statement, “The vaginal microbiome plays an important role in regulating vaginal health and disease and has a major impact on prenatal health.

“Our human vagina chip offers an attractive solution to study host-microbiome interactions and accelerate the development of potential probiotic treatments.”

The technology, funded by the Bill and Melinda Gates Foundation, focuses on treating BV because it doubles the risk of contracting sexually transmitted diseases, including HIV, and increases the likelihood of preterm birth in pregnant women.

BV is caused by an imbalance of bacteria in the vagina, which can result in gray-colored discharge with a fishy smell.

The vagina should typically be dominated by the Lactobacillus species, which protects the host from infection.

But in patients with BV, it is overtaken by an overgrowth of an organism called Gardnerella vaginalis and anaerobic bacteria. “Anaerobic” means that bacteria do not need oxygen to survive or grow.

This upsets the balance of natural chemicals in the vagina, which may not be obvious when there are no symptoms.

BV is currently treated with antibiotics, but it often recurs and can lead to more serious complications, including pelvic inflammatory disease and even infertility.

Scientists look for more advanced systems to test drugs and decide to create their own “vagina”.

The organ-on-a-chip consists of human vaginal epithelium and underlying connective tissue cells that replicate many of the physiological features of the vagina and can be inoculated with different strains of bacteria to study their effects on organ health.

The team placed the human vaginal cells on a polymer chip and then added human uterine fibroblast cells on the opposite side of the permeable membrane separating the upper and lower canals.

And this produced a replica of the human vaginal wall.

In just five days, the team noticed that the vagina chip had different layers of cells that corresponded to those found in human vaginal tissue.

Adding the female sex hormone estradiol (a form of estrogen) to the structure altered the chip’s gene expression in a way that shows it is sensitive to hormones.

The next step was to test the innovation against BV by infecting the chip with three different BV bacteria.

The organ-on-a-chip consists of human vaginal epithelium and underlying connective tissue cells that replicate many of the physiological features

A consortium of these three “bad” microbes caused the chips’ pH to rise, damaging vaginal epithelial cells and significantly increasing the production of several pro-inflammatory cytokines — all responses similar to those seen in human patients with BV.

Abidemi Junaid, Ph.D., a research scientist at the Wyss Institute, said in a statement, “It was very striking that the different microbial species had such opposite effects on human vaginal cells, and we were able to observe and measure these effects quite easily our vagina chip.

“The success of these studies demonstrates that this model can be used to test different combinations of microbes to help identify the best probiotic treatments for BV and other conditions.”

The team is now using the vagina chip to test new and existing treatments for BV to identify effective therapies that can move into clinical trials.

The new vagina on a chip is being touted as a solution because the team at Harvard University’s Wyss Institute claims it replicates the microenvironment of human vaginal tissue, including its microbiome in vitro

They are also working to integrate immune cells into the chip to study how the vaginal microbiome might drive systemic immune system responses.

Don Ingber, MD, Ph.D., founding director of the Wyss Institute, said: “There is a growing recognition that concern for women’s health is vital to the health of all people, but the creation of tools to study the female human physiology is lagging.

“We hope that this new preclinical model will advance the development of new treatments for BV, as well as new insights into women’s reproductive health.”

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