Bioengineer Mats Hellström, PhD, spends most of his days working with mice, rats, and petri dishes full of cells. Although he sees no patients, his work has the potential to impact the lives of thousands, if not millions, of women diagnosed with infertility: He’s working toward creating a lab-grown uterus.
Hellström, an associate professor in bioengineering and organ regeneration at the University of Gothenburg in Sweden, originally studied the regeneration of the nervous system, but he became interested in the reproductive system after meeting Mats Brännström, MD, PhD, a pioneer in the field of uterine transplantation. Their goal, Hellström says, became “to create a bioengineered organ to replace the need for a donor.”
“I was at that age where having kids becomes interesting,” he tells Future Human. “It all sounded really, really fascinating.”
Hellström’s work could help women with uterine factor infertility, the kind caused by problems in the structure or function of the uterus. It isn’t the most common cause of infertility, but it’s not especially rare, either, affecting an estimated one in 500 reproductive-age women. While it can sometimes be addressed with surgery, women with this type of infertility generally have limited options if they want to give birth to children. On top of that, infertility can negatively impact their mental health and quality of life. “I think most people really underestimate the psychological effect of infertility,” says Alice Domar, PhD, a health psychologist at the Beth Israel Deaconess Medical Center in Boston, whose 1993 paper showed that women with infertility had equivalent levels of anxiety and depression to women with cancer, AIDS, and heart disease. “For infertility patients,” she says, “infertility affects every area of their lives.”
As factors like financial instability and pursuit of career goals cause women to increasingly delay having children, infertility could become even more common in the future. Infertility is also an issue for trans women hoping to have children, although research on uterine transplants has recently opened that up as a future possibility.
“I think most people really underestimate the psychological effect of infertility.”
Uterine transplants from living and deceased donors are an option for women with uterine factor infertility, but they’re risky. Rejection of the uterus is common, and even when the transplant is successful, it doesn’t always result in the birth of a child. Recipients must take immunosuppressant drugs, which keep their immune systems from attacking the donated organ but can also cause kidney damage and make them susceptible to serious infections.
A lab-grown uterus, made from the patients’ own cells, would eliminate the need for both donors and immunosuppressant drugs.
Growing an entire organ — especially one that can withstand massive changes during pregnancy and birth — is a complex endeavor. It requires many different types of cells and an intricate network of blood vessels. To obtain all of these cells, scientists must either harvest them from the person’s body or develop them from stem cells. These cells are then grown on a structure, known as a scaffold, that holds them in the right place.
Since the uterus is so complex, scientists are starting by creating small pieces of it and applying these patches to damaged organs. In 2016, Hellström and colleagues used small pieces of bioengineered uterine tissue to repair uterine damage in rats. In 2020, a team led by Anthony Atala, MD, the director of the Wake Forest Institute for Regenerative Medicine, used a larger patch of bioengineered tissue to reconstruct part of a rabbit uterus, resulting in several healthy baby rabbits.
Since the field is so new, every lab takes its own approach to growing these patches. “We all use different strategies,” Hellström says. “Different types of scaffoldings, different types of cells. No one really knows the best [way], at the moment.”
Atala’s group harvested two different types of cells from each rabbit’s uterus, let the cells grow in petri dishes, and then used them to seed a synthetic scaffold made of biodegradable mesh. Hellström’s group used a mixture of mostly stem cells with some uterine cells. Their scaffold consisted of a piece of an actual uterus from which all the cells have been removed, leaving only the connective material.
Stem cells can turn into many different cell types, making them useful for bioengineering. But convincing them to develop into a specific type of cell is tricky. Hellström says that scientists don’t yet know the precise combination of ingredients to turn stem cells into different types of uterine cells.
Hellström was hoping the uterine cells in his mixture would influence the stem cells to become uterine cells as well, but that’s not what happened. Instead, after the bioengineered tissue had been implanted into a living rat uterus, the stem cells seemed to stimulate the rat body to repair its own uterus.
“It’s one of those things where you never say never in the future.”
Both Hellström and Atala say that the next steps are clear. “The main thing now is to go to a larger [animal] model, so we can keep replicating these findings, so hopefully someday we can take this to humans,” says Atala. Hellström’s team has already started experiments using bioengineered uterine tissue in sheep.
Though bioengineering an entire uterus, even in animals, is still a long way off, scientists could apply their discoveries to human medicine much sooner. Bioengineered tissue patches, says Atala, could help women with abnormal uterine development by providing extra uterine tissue to repair malformations. They could also be used to repair uterine scarring that can occur after surgeries like cesarean sections or placental tumor removal, notes Hellström.
While extensive testing is still needed to ensure safety, these patches could potentially be in human trials in as little as five to 10 years, he says.
Bioengineering a whole uterus is much further down the line. And until scientists figure out how to make stem cells differentiate into uterine cells, any uterine bioengineering technology will be limited to people who have at least a partial uterus from which uterine cells can be harvested and grown.
In addition to helping women with congenital disorders that cause them to be born without a uterus, being able to bioengineer a complete uterus using stem cells could also be relevant for trans women. The key will be figuring out whether stem cells with a Y chromosome can be induced to become uterine cells; trans women have X and Y chromosomes, whereas cis women have two Xs.
“It’s one of those things where you never say never in the future, but right now it’s not where the technology is at this moment,” says Atala. But just because it hasn’t been accomplished yet doesn’t mean it will never be; the field of bioengineering is moving forward at a blistering pace.
Research centered on different aspects of infertility is also gaining more support, albeit more slowly. Historically, says Domar, research on the uterine elements of infertility has been lacking, especially given the emphasis on sperm and egg quality. “A lot of people feel the uterus is sort of in the forgotten zone,” she says. For many women with uterine factor infertility, having a surrogate carry their child may be their only way to have children that are genetically their own. Yet surrogacy is not an easy process; it can be fraught with financial, legal, ethical, and emotional troubles. “I think it’s really great that somebody is trying to figure out ways to fix the uterus,” says Domar.
And although a bioengineered uterus may seem far-fetched, she reminds us: “IVF was a pipe dream 50 years ago.”