Scientists create world’s first ‘Vagina-on-a-Chip’ to combat bacterial diseases
Researchers at the Wyss Institute at Harvard University have engineered the first-ever "Vagina on a Chip" in the world that replicates the human vaginal tissue microenvironment in vitro, Scientific American reported on Wednesday.
It is composed of the human vaginal epithelium and underlying connective tissue cells and it replicates many of the physiological features of the vagina, according to Harvard.
Studying vaginal health
Best of all, it can be inoculated with different strains of bacteria allowing researchers to study their effects on the organ’s health.
“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,” said first author Gautam Mahajan, Ph.D., a former Wyss Institute researcher who now works at Emulate, Inc.
The Vagina on a Chip was developed with funding from the Bill and Melinda Gates Foundation to treat vaginal microbiome disruptions caused by bacterial vaginosis (BV).
The organization hopes to create a biotherapeutic treatment for BV and move it into human clinical trials to decrease its many negative side effects, such as infections of the reproductive tract, prenatal complications, and infant death rates, particularly in low-resource nations.
BV is currently treated with antibiotics, but it often recurs and can lead to more serious complications, including pelvic inflammatory disease and even infertility.
“A major stumbling block for that effort was that there were no good preclinical models that could be used to study which therapies can actually treat BV in human tissues. Our team’s project was to create a human Vagina Chip to aid in the development and testing of new therapies for BV,” said co-author Aakanksha Gulati, Ph.D., a Postdoctoral Researcher at the Wyss Institute.
Making the chip
To make the chip, the team combined the microfluidic Organ Chip platform developed at the Wyss Institute with human vaginal epithelial cells and human uterine fibroblast cells, essentially replicating the structure of the human vaginal wall.
After just five days, the Vagina on a Chip had developed differentiated cells that matched those found in human vaginal tissue. The scientists then introduced the female sex hormone estradiol (a form of estrogen) into the Vagina Chip and found that the chips’ gene expression patterns changed in response.
They had successfully created a living model of the human vagina. This process was then further tweaked to allow for the study of the vaginal microbiome and its many bacteria.
Scientists found that beyond helping to maintain an acidic environment, the presence of the L. crispatus bacteria also affected the Vagina Chip’s innate immune responses.
They also noticed that chips with bacterial consortia produced lower levels of several inflammation-causing cytokine molecules than chips without the bacteria.
“It was very striking that the different microbial species produced such opposite effects on the human vaginal cells, and we were able to observe and measure those effects quite easily using our Vagina Chip,” said co-author Abidemi Junaid, Ph.D., a Research Scientist at the Wyss Institute.
“The success of these studies demonstrate 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 chip is described in a new paper published in Microbiome.
A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.