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Designs on stem-cell based "neovagina" take $1 million Magee Prize
Illustrated by
Elena Cerri and Shaniel Bowen

The latest Magee Prize shines a light on the need for better options for vaginal wellness.

Apparently, even people who’ve dedicated their careers to women’s health research can get fussy about the “V” word.

Pamela Moalli gave a presentation recently on her work and chuckles at the recollection. “Initially, we were asked to tone down our talk and just refer to it as ‘the female organ,’ and I said, ‘Well, which one?’”

Moalli, University of Pittsburgh professor of obstetrics, gynecology and reproductive sciences, leads a team that won the $1 million Magee Prize in November 2021. The prize, awarded to an international team, was created to promote knowledge and enhance the health and wellness of women and infants worldwide; it’s sponsored by the Richard King Mellon Foundation.

Though many women and girls struggle with vaginal wellness—“It’s just not talked about openly,” notes Kyle Orwig, Pitt professor of obstetrics, gynecology and reproductive sciences who is a project coinvestigator.

Orwig, a PhD, and Moalli, an MD, PhD, are both members of the Magee-Womens Research Institute. Caroline Gargett, a PhD from Monash University in Australia, has joined them in their studies of vaginal stem cell populations as a possible basis for regenerative medicine solutions. Krystyna Rytel, an undergraduate at Pitt, is also on the team.

The group will use the prize funds to develop new biomaterials for repairing tissue loss in women with compromised vaginal structure and function. If successful, the work could have sizeable therapeutic potential:

Congenital Defects
Each year, one in 5,000 girls in the United States is born without a vagina. Current reconstruction techniques involve grafts of skin or intestinal tissue. In terms of sensation and function, both are problematic.

Cancer Treatment
Surgical treatment of genital, bladder, breast, colorectal and ovarian cancers, as well as chemotherapy and radiation treatment, can result in structural and functional damage. That damage can affect hormones (leading to abrupt menopause) and impair self-image, relationships and normal activities of daily living. Each year, hundreds of thousands of women are diagnosed with these cancers.

Aging and Menopause
Today’s long-term solutions to vaginal dryness and other age-related changes pose issues. Hormone supplements, even when used locally, are contraindicated in women with serious blood clotting disorders and those with certain hormone-responsive cancers.

Lubricants might enhance sexual function, but the results are transitory. Laser treatments are painful, and they can be toxic to vaginal cells.

The bottom line, so to speak? Current therapies to restore vaginal anatomy, structure and function don’t work well enough. That’s where Moalli and colleagues’ neovagina comes into the picture.

It starts with stem cells

Vaginal changes throughout the life cycle—during menstruation, for instance—are “pretty strong evidence the vagina is dependent on a population of stem cells,” says Orwig. The team wants to tap into this natural reservoir.

Other studies often neglect what are known as niche cells, which form the environment in which stem cells form, says Moalli. “They are the soil which allows the stem cells to engraft and proliferate. Without the correct soil or niche, stem cells do not survive.”

For one study, the team will acquire samples from healthy women, as well as from women with vaginal malformations or cancer survivors—patients like those Moalli sees in the clinic.

In preclinical studies, mice will be subjected to chemotherapies routinely used to treat cancers of the breast and reproductive tract. These regimens deplete local stem cell populations, including those that maintain vaginal health.

The researchers will then transplant vaginal stem cells and their niche cells into these stem cell–depleted mice to determine exactly what’s needed for engraftment.

The team is already making progress and may be the first to characterize stem cell populations found within the full thickness of vaginal tissues.

In time, Moalli hopes to use their findings to improve on existing therapies by growing neovaginas. So, how would they do this?

First, they’d reprogram stem cells and their niche cells (from the patient), then graft these neovagina seeds back into the patient. This could happen either by injecting masses of new vaginal stem cells directly into the patient (preclinical experiments indicate some stem cells can begin to build new organ structures on their own) or by placing the stem cells onto a scaffold made from donor vaginal tissue.

This method might be extended to transwomen for gender-confirming surgeries. For survivors of hormone-dependent cancers, the team aims to understand how to activate remaining stem cell populations to restore hormonal function.

“The vagina has tremendous regenerative potential,” says Moalli, explaining that even severe childbirth injuries can often heal with little, if any, scarring. “If we can biofabricate kidneys and livers, we most certainly can make vaginas.

 “It’s really hard to sit across from these people who are hurting and say, “We don’t have any options for you.’”