When the Taylor lab in Yale’s Division of Reproductive Sciences extracted stem cells from human endometrial tissue—more commonly known as the uterine lining—the researchers were proud of their accomplishment. They didn’t think the find was extraordinary, and they certainly didn’t imagine that it might lead to treatments for a neurodegenerative condition. They were wrong—and happily so.
“The best discoveries throughout the history of science have not been predictable, have not always come out the way we anticipated they would, or the way we designed them to,” says Hugh Taylor, MD, HS ’92, FW ’98, chair and the Anita O’Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences, and professor of molecular, cellular, and developmental biology. “That’s the real excitement in science—when it doesn’t follow the predicted path, when you get a surprise.”
The surprise, in this case, wasn’t finding the multipotent stem cells but finding their proclivity to differentiate into dopaminergic neurons: the brain cells whose loss in Parkinson’s disease leads to tremor, speech difficulty, poor balance, and a host of other symptoms. A reproductive sciences laboratory like Taylor’s is not where one would expect to find a treatment for Parkinson’s disease.
“There certainly aren’t dopaminergic neurons in the uterus,” Taylor says.
Though unintended, the discovery has been serendipitous and is unfolding quickly; so far, the team has demonstrated the neurons’ ability to boost fallen dopamine levels in mouse and primate models of mild Parkinson’s disease. In future studies, the team hopes to examine more severe forms of the disease to identify the therapy’s effects on physical symptoms beyond improving dopamine levels.
The stem cells’ tendency to differentiate into dopaminergic neurons is as yet unexplained, but Taylor and his colleagues have also coaxed the cells into becoming insulin-producing beta cells. Trials in mouse models have used endometrial stem cells to produce beta cells that continued producing insulin and stabilized blood-glucose levels within five weeks when injected into diabetic mice.
Taylor credits the cascading discoveries not only to his team and colleagues in other departments but to the collaborative atmosphere that facilitates the researchers’ interactions. “For each of these applications [of endometrial stem cells], we found the world’s expert right in our backyard,” he says. “You have world-leading experts in these diseases right down the hall, or in the building across the street, who are more than glad to help advance colleagues’ research as collaborators.” It helps that stem cells are a valuable currency across all of medicine because of their unique ability to produce myriad different cell types—when given the right environment. The endometrium, regenerating month by month for years, is just such an environment.
While adult stem cells reside in many different tissues, finding and extracting them in great numbers is challenging and—in all instances but one—invasive. The endometrium is the only tissue from which adult stem cells can be retrieved via a routine office-based procedure without anesthetic. This source is not limited to women of reproductive age, either: estrogen treatment can stimulate endometrial growth in women of all ages. Treatments that use a patient’s own cells are attractive because they eliminate the risk of tissue rejection. Taylor envisions tissue banks that would use material retrieved from hysterectomies to obtain additional stem cells. These could then be used to treat people without a uterus.
“There are tremendous applications in almost all fields of medicine. I think the sky’s the limit, really,” Taylor said. “Any disease where cells become defective or die, we can consider using stem cells to replace them.” Parkinson’s disease and diabetes are only two of thousands of medical conditions that could one day be treated—or cured—with cell-based therapies.
“Stem cell research has shown potency; it has tremendous potential,” Taylor said. “I think that cell-based therapy can do things that drugs could never do, and I think we’ll see a lot more cell-based therapies on the horizon.”