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Artificial ovary grown using 3-D Petri dish

BROWN (US)—Scientists have invented the first artificial human ovary and successfully used the lab-grown organ to mature human eggs.

The advance provides a potentially powerful new means for conducting fertility research and could also yield infertility treatments for cancer patients. Details are reported in the Journal of Assisted Reproduction and Genetics.

“An ovary is composed of three main cell types, and this is the first time that anyone has created a 3-D tissue structure with triple cell line,” says Sandra Carson, professor of obstetrics and gynecology at Brown University.

Carson, the study’s senior author, says the ovary not only provides a living laboratory for investigating fundamental questions about how healthy ovaries work, but also can act as a testbed for seeing how problems, such as exposure to toxins or other chemicals, can disrupt egg maturation and health.

Clinically, the artificial ovary could play a role in preserving the fertility of women facing cancer treatment in the future, says Stephan Krotz, a Houston fertility doctor who is the paper’s lead author and a former fellow in Carson’s lab.

Immature eggs could be salvaged and frozen before the onset of chemotherapy or radiation, he said, and then matured outside the patient in the artificial ovary.

Building an ovary
What makes the artificial ovary a functional tissue, rather than just a cell culture, is that it brings all three ovarian cell types into a 3-D arrangement similar to a real ovary in the body.

The means for making such compositions of cells was invented in the lab of Jeffrey Morgan, associate professor of medical science and engineering and a coauthor of the study.

His so-called 3-D Petri dishes are made of a moldable agarose gel that provides a nurturing template to encourage cells to assemble into specific shapes.

To create the ovary, the researchers formed honeycombs of theca cells, one of two key types in the ovary, donated by reproductive-age (25-46) patients at the hospital.

After the theca cells grew into the honeycomb shape, spherical clumps of donated granulosa cells were inserted into the holes of the honeycomb together with human egg cells, known as oocytes. In a couple days the theca cells enveloped the granulosa and eggs, mimicking a real ovary.

The big test, however, was whether the structure could function like an ovary—namely to mature eggs. In experiments the structure was able to nurture eggs from the “early antral follicle” stage to full maturity.

“[This] represents the first success in using 3-D tissue engineering principles for in vitro oocyte maturation,” the researchers write in the journal article.

Carson says her goal was never to invent an artificial organ, per se, but merely to create a research environment in which she could study how theca and granulosa cells and oocytes interact. When she learned of Morgan’s 3-D Petri dishes, they began to collaborate on creating an organ. Morgan says this is the first fully functional tissue to be made using the method.

The work was supported by the Rhode Island Science and Technology Advisory Council and from the Women & Infants Hospital of Rhode Island.

More news from Brown University: http://news.brown.edu/

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