Egg Stem Cells

Today, a woman’s fertility is limited 
by her total supply of eggs and by the diminished quality of those eggs as she reaches her 40s. Tilly’s work with the stem cells—cells that can differentiate, or develop into other kinds of cells—could address both issues. For one thing, it’s possible that these newly discovered cells could be coaxed to develop into new eggs. And even if not, he says, they could be used to rejuvenate an older woman’s existing eggs.

Tilly first found egg stem cells in mice in 2004. Once he identified egg stem cells in ovarian tissue from adult women, he isolated the cells and injected them into human ovary tissue that was then transplanted into mice. There the cells differentiated into human oocytes, the immature egg cells that mature, one at a time, at ovulation. Tilly didn’t take these oocytes any further, but he says he has gotten egg stem cells from mice to generate functional mouse eggs that were fertilized and exhibited early embryonic development.

The research is still a long way from creating a crying human newborn. Nevertheless, the paper “changes what we understand” about fertility, says Tilly, who also directs a center for reproductive biology at Massachusetts General Hospital. Though some of Tilly’s peers remain dubious that the cells he’s found in women’s ovarian tissue are actually stem cells or could become functional egg cells, many find the research provocative. “I think this is a very intriguing leap,” says Elizabeth McGee, an associate professor and head of reproductive endocrinology and infertility at Virginia Commonwealth University. “However, I think there’s still a long way to go before this becomes a useful product for women.”

Boston-based OvaScience, which is commercializing Tilly’s work, hopes it won’t be too long. The company’s cofounders include venture capitalist Christoph Westphal and Harvard antiaging researcher David Sinclair, who founded Sirtris Pharmaceuticals and sold it to GlaxoSmithKline for $720 million in 2008. OvaScience has raised $43 million to pursue fertility treatments and other applications for the stem cells.

One of the more tantalizing implications is that this technology could be used to reclaim the youth of an older woman’s eggs. Tilly says he can do this by transferring mitochondria—the cell’s power source—from the stem-cell-derived cells into the existing eggs. Researchers who tried something similar in the 1990s, with the help of young donors, found that mitochondria from the donors’ egg cells could improve the viability of older eggs. But the nearly 30 children who resulted from this work ended up with DNA from two women as well as their father. (It’s not clear whether the children suffered any health consequences.) By being her own source for the younger mitochondria, a woman could avoid that potentially dangerous mix of DNA, Tilly says.

David Albertini, director of the Center for Reproductive Sciences at the University of Kansas Medical Center and a member of OvaScience’s advisory board, says he “can’t wait to get [his] hands on” Tilly’s cells for his own egg research. But he says it’s too soon to consider implanting them in women before much more testing is done in mice.