Thursday, October 4, 2012

Mouse eggs created from stem cells for the first time

Mouse eggs can now be cooked up from scratch. Using stem cells, a Japanese team has created healthy eggs that, once fertilised, grow into normal mouse pups.

Both egg and sperm cells start life as primordial germ cells (PGCs). Last year, Katsuhiko Hayashi and his colleagues at Kyoto University in Japan found they could generate PGC-like cells from either mouse embryonic stem cells or body cells that can turn into stem cells ? known as induced pluripotent stem cells or IPSCs. What's more, the team managed to coax these PGC-like cells into becoming sperm (Cell, DOI: 10.1016/j.cell.2011.06.052).

Now Hayashi and his colleagues have created eggs from the PGC-like cells. They started with embryonic stem cells and IPSCs taken from a female mouse embryo. In separate experiments, the team coaxed each type of stem cell to form PGC-like cells. When these cells were surrounded by ovary cells, also taken from a mouse embryo, they formed immature egg cells.

The team implanted these young egg cells into the ovaries of adult mice. Four weeks later, when Hayashi's team removed the ovaries, they found the cells had developed into mature eggs. When these eggs were fertilised with sperm and implanted into other mice, they were able to form embryos that developed into healthy mouse pups.

"It's an amazing result," says Evelyn Telfer at the University of Edinburgh, UK, who was not involved in the work.

The success of the PGC-like cells suggests that these induced cells are very similar to the PGCs found in the body, says Hayashi. It's difficult to study PGCs themselves because they are so rare, says Hayashi.

"We will be able to identify factors involved in PGC development," he says. "We expect that some of these are [the same] in humans [as in mice], and that they are responsible for human disease."

Abnormalities

Unfortunately, not all of the embryos developed normally. The team couldn't tell whether the abnormalities were a result of problems with the egg cells themselves or their growth environment. "[They'll] need to optimise the system," says Telfer.

Once the wrinkles have been ironed out, it would be possible, in theory, to fertilise stem-cell-derived eggs with stem-cell-derived sperm, Telfer says. "If you took the stem cells from the same individual you could avoid sexual reproduction," she says, half-jokingly.

In the meantime, stem-cell-derived egg and sperm cells hold the most promise for people with fertility problems. If the team can derive egg and sperm cells from adult stem cells, individuals who have become infertile ? because of harsh cancer therapies for example ? could potentially generate new sperm or eggs from their own body cells.

Journal reference: Science, DOI: 10.1126/science.1226889

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