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New stem cell technique — no embryos used

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Only women could be treated with unfertilized egg method

Scientists have found a way to make stem cells from unfertilized eggs, suggesting a potential alternative to controversial and technically difficult embryo cloning.

A group at Harvard University led by research fellow Kitai Kim and stem cell pioneer George Daley, an adviser to the California Prop. 71 stem cell program, reported success Thursday with the new method using mouse eggs. Similar experiments with human eggs are under way.

The goal is to make stem cells from a particular patient — or stem cells that carry a particular set of genes — in order to make pancreatic cells to treat diabetics or neurons to treat people with incurable brain disorders. Cloning, or somatic cell nuclear transfer, may be one way to do this, but the new method appears to be easier.

Deriving stem cells from unfertilized eggs without cloning offers “another way to generate cells that might be suitable for transplantation,” Daley said during an interview.

“It’s a very efficient process,” he said, adding that although it hasn’t been achieved yet in humans, “there is no theoretical reason” the mouse experiments can’t be duplicated using unfertilized human eggs.

Results were described Thursday in the online edition of the journal Science in mostly dry technical language. But the experiments also put a new twist on some of the central ethics questions confronting regenerative medicine, such as what qualifies as an “embryo” and whether cloning is even necessary.

The new stem cell recipe mimics the early steps in a type of reproduction common in some species of invertebrates, fish and reptiles. Known as parthenogenesis, a term derived from the Greek for “virgin birth,” it allows females to produce offspring without need of a male to fertilize the egg.

Parthenogenesis is considered virtually impossible for mammals, although laboratory attempts have been made. Now, it seems it might be a strategy for high-tech medical repairs.

One catch: It would work only for the half of the population that produces eggs.

“It’s only good for women,” said Arlene Chu, director of scientific activity at the Prop. 71 stem cell agency, known as the California Institute for Regenerative Medicine.

Scientists are trying to produce stem cell lines from the cellular precursors of sperm, but that’s more technically challenging than using eggs, which are larger and biologically more stable. So there’s no immediate prospect of a male counterpart to the female-only stem lines described in the latest study.

This raises the prospect — still science fiction — that a hospital might be able to treat a woman’s spinal cord injury by extracting her eggs and turning them into stem cells, which then might be made into neurons or other cells for injection at the injury site. A man with the identical injury would be out of luck.

“We haven’t had to confront this before,” said Hank Greely, a Stanford University bioethics specialist. “We still have to figure out some way to deal with the guys.”

Even for women, the Harvard experiments are only a first step.

The scientists took care to derive stem cells essentially matching the immune system of the female from which the eggs were taken. In a human patient, this would ensure that transplant cells wouldn’t be rejected as foreign material.

The new stem cells appeared capable of producing many types of mature cells, but they may not be as flexible as stem cells produced in the traditional way, and they may generate medical risks, including cancer, if transplanted, researchers said.

But designer stem cell lines may be important for reasons beyond transplants.

One idea is to create disease-specific stem cells engineered to contain the same genes that give rise to such incurable killers as Alzheimer’s or diabetes. Those stem cells could be used to study how those diseases develop, and also to test treatments that might stop an ailment even before symptoms appear.

Another path to the same goal is cloning, in which a patient’s DNA might be inserted into an egg whose own nucleus has been removed. If the transfer works as intended, the egg would reprogram the new nucleus, creating a cloned embryo.

Daley and other labs, including scientists at UCSF, are trying to produce cloned stem cell lines this way, so far with no reported success. In contrast, Daley and his colleagues produced 72 stem cell lines in 150 attempts in the mouse experiments reported Thursday.

Susan Fisher, a stem cell biologist at UCSF, said it’s unlikely that human eggs will prove as cooperative as the mouse eggs, noting that mice are far more efficient reproducers than primates.

“I still believe this work strongly suggests it would be possible in humans, and that’s quite exciting,” Fisher said. “It looks to be a robust technique.”

Cloning raises ethical objections because human embryos made that way theoretically could develop into a cloned infant, with DNA identical to the person who provided the nucleus, in much the same manner that cloned animals have been produced.

The latest mouse experiments create what are known as “parthenotes,” which may or may not even qualify as “embryos” depending on one’s definition of that term. There is no evidence that a human or even a true mouse parthenote could develop into a viable fetus, even if successfully implanted in the womb.

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