In a study appearing Friday in the journal Science, researchers at the University of Pennsylvania said they were able to cause stem cells from mouse embryos to transform into oocytes, or eggs, and then to further develop into primitive embryos.
"Most scientists have thought it impossible to grow gametes (eggs and sperm cells) from stem cells outside the body," said Hans R. Scholer of the school of veterinary medicine at the University of Pennsylvania.
Scholer said the spontaneous embryos could not be used to reproduce mice because they contain an incomplete set of chromosomes, but the eggs probably could be used for cloning.
Embryonic stem cells can grow into virtually any cell in the body. Some researchers have suggested they could be used to grow new heart, liver, brain or pancreas cells that then could help revive or repair ailing organs.
To make these new organ cells compatible with a patient, researchers say they would have to clone an embryo using the nucleus from a cell of the patient. At an early stage of development, the new stem cells would be removed and grown into the target cells.
The process kills the embryo. There would have to be a large supply of human eggs for this technique to be medically useful for the millions of people who could benefit. Right now, those eggs are only available from female donors who face a sometimes painful harvesting procedure.
The study by Scholer and his co-authors suggests that eggs possibly could be made in the laboratory from stem cells. This would avoid the need for donors — addressing one of the ethical concerns about using human embryonic stem cells for medical treatment — and lead to an almost limitless supply.
"We would like to use these oocytes as a basis for therapeutic cloning and hope that our results can be replicated with human embryonic stem cells," said Scholer.
In a statement in Science magazine, bioethicist Arthur Caplan of the University of Pennsylvania said the Scholer study is "an ethical earthquake." He said it answers one ethical concern about therapeutic cloning — using harvested eggs to make embryos and then destroying the embryos to get stem cells for treatment. But he said the research will increase the concern of people who are fundamentally opposed to embryonic stem cell studies.
Legislation that has passed the House forbids human cloning for any purpose. A similar bill is in the Senate. President Bush has said he favors the ban.
Alan Spradling of the Carnegie Institution of Washington said in Science that to prove the eggs produced from stem cells are normal, researchers must show that the eggs can be fertilized and then used to produce normal offspring by implanting them in mother mice.
Scholer said that is the next step planned by his research group.
Thaddeus G. Golos, a stem cell researcher at the University of Wisconsin, said the study is an important advance, but cautioned that it was too early to draw any conclusions regarding human eggs.
"There are many differences between human and mouse embryonic stem cells," he said. "Judgment should be withheld at this time for the therapeutic potential."
Ronald McKay, a stem cell researcher at the National Institutes of Health, said he was surprised and fascinated by the results of the experiment.
"None of us anticipated" that embryonic stem cells could be coaxed to develop into eggs and embryos, said McKay. He said the results are "fabulous" scientifically because it gives researchers a new way of studying a very fundamental step in reproduction.
In the study, Scholer and his co-authors put into stem cells a gene that would prompt a glow from a fluorescent marker if the cells begin turning into egg cells.
After a few days, the cells transforming toward eggs cells formed clumps and then individual cells coated with follicle-like cells similar to the tissue surrounding normal eggs in female mammals.
In a process that resembled ovulation, the oocytes were released by the follicle cells on day 26, Scholar said. The oocytes went on to form embryos in a process called parthenogenesis, or reproduction without sperm fertilization. Scholer said such embryos generally are not viable, but he believes the eggs may be normal.