The researchers broke ovarian cells out of human tissue using enzymes, and poured them into a mold made of agar, a gelatinous substance usually derived from algae. The different types of cells then assembled themselves into a honeycomb shape, with the theca and granulosa cells forming the structure. The egg cells, or oocytes, were inserted inside and bathed with hormones to stimulate the theca cells to produce androgen, and the granulosa cells to make estrogen.
“We took a different tack to rely on the inherent adhesiveness of cells to drive self-assembly,” says Jeffrey Morgan, codirector of the Center for Biomedical Engineering at Brown, who led this aspect of the research. “In that nonadhesive environment, the cells will stick to each other and self-assemble a three-dimensional structure, and it conforms to the shape of our mold.”
Researchers had assumed that, if allowed to self-assemble, cells would form a sphere, but Morgan says he showed that they can also create more complex forms with a little prompting.
Kim L. Thornton, a reproductive endocrinologist at Boston IVF, one of the nation’s largest fertility centers, says it’s tricky to re-create in a lab all of the activities that go on in a woman’s ovaries. “One of the challenges with maturation is, there are lot of things that go on locally that may affect the ability of oocytes to become mature,” she says. “We can’t duplicate all of those conditions” in a lab dish. However, Thornton says, the Brown model “is interesting, and it’s certainly promising.”
Carson says that now that the team has created the model, she wants to go back and look more closely at how it functions. She would like to identify various proteins involved in egg maturation, and be able to explore whether those proteins can be altered as a means of contraception. “We could also theoretically find something that might be important in the development of ovarian cancer,” she says.
The work can also be used to test for toxic effects from everyday products, such as plastics and insecticides, as well as medications–“anything we might be able to test against the control,” Carson says. “We’re not there yet, but I think this is going to be the most powerful use of the model.”