In an important step for research on women’s reproductive health, scientists have developed a cervix-on-a-chip, a lab model replicating the human cervix's structure and function.
Biotechnology research in a lab – illustrative photo. Image credit: CDC via Unsplash
The team, led by researchers at Harvard Medical School, Boston Children’s Hospital, the Wyss Institute for Biologically Inspired Engineering at Harvard University, and the University of California, Davis, used microfluidics to build a model of the cervix that captures the complex interactions between different cervical cell types.
The scientists plan to use the model in conjunction with their earlier vagina-on-a-chip to develop and test treatments for bacterial vaginosis and other diseases that affect the female reproductive tract.
“We created a platform that now enables researchers to find answers to additional long-standing questions in women’s health,” said senior author Donald Ingber, founding director of the Wyss Institute, the HMS Judah Folkman Professor of Vascular Biology at Boston Children’s, and the Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
The team describes the model in a study published in Nature Communications.
The potential of organs-on-chips
Scientists have long been intrigued by the idea of creating organs-on-chips, which consist of miniature tissues grown on microfluidic chips that mimic the structure and function of human organs. Such models enable testing that can’t be done on human organs or in other lab settings, and may reduce the need for animal models — making them a valuable tool for advancing research and accelerating drug development.
Ingber and his team are interested in developing organs-on-a-chip for different female reproductive organs. They hope that such models can counter a historical lack of research on women’s reproductive health, which has led to an inadequate understanding of common diseases of the female reproductive tract.
In particular, they want to use their models to study bacterial vaginosis, an infection caused by a bacterial imbalance in the vagina and cervix that affects more than 25 percent of reproductive-age women worldwide.
Left untreated, bacterial vaginosis can cause severe discomfort as well as complications such as increased risk of sexually transmitted infections, higher rates of miscarriage and preterm birth, pelvic inflammatory disease, and infertility. However, current treatment is limited to antibiotics that often fail to kill the invading bacteria, leading to recurrence in more than 60 percent of women.
In 2022, Ingber and colleagues developed a vagina-on-a-chip that reproduces many of the physiological features of the vagina, including its community of microorganisms known as the microbiome. They have since used the model to study how the vagina is affected by different strains of bacteria, including those that cause bacterial vaginosis. The cervix-on-a-chip builds on this work.
How the cervix model works
The new model consists of the two major cell types in the human cervix: epithelial cells, which make up the tissue that lines the organ, and fibroblasts, cells that produce key structural and connective proteins such as collagen.
The researchers combined layers of these cell types to reproduce the cervical wall, which they differentiated into the upper and lower cervical canals.
They also replicated the mucus production of the cervix, including how mucosal features change in response to sex hormones.
The team reports that observations in the cervix-on-a-chip align with those in human patients and that the model is opening new windows into biology.
“Our engineered cervix model and the breadth and depth of analysis it allows sets a new standard in research that is well in line with existing clinical observations, while offering the first new insights into cervix functionality and vulnerability,” said first author Zohreh Izadifar, HMS instructor in surgery at Boston Children’s.
To test their model, the researchers exposed it to healthy and unhealthy cervical bacteria. They found that healthy bacteria increased the thickness and improved the quality of the mucus layer and left the epithelial layer intact. By contrast, unhealthy bacteria compromised the function of the epithelial layer and increased production of proteins associated with pathogenic processes, including inflammation.
Ingber hopes that the cervix-on-a-chip can be used alongside the vagina-on-a-chip to evaluate potential treatments for bacterial vaginosis and even identify new treatments for other diseases that affect the female reproductive tract.
Source: HMS