A bioethics twist: artificial stem cells

New procedure lets adult mouse cells mimic stem cells, bringing hope to anticloning activists.

Scientists in the United States and Japan announced yesterday that they have developed artificial stem cells from adult mouse cells. If the approach can be retooled for humans, they say, it would avoid the ethical quicksand that surrounds the use of stem cells drawn from nascent human embryos.

Current stem-cell extraction methods destroy these embryos, which during the procedure are microscopic, hollow balls of cells only a few days old. For people who hold that human life begins at the moment of conception, destroying an embryo at any stage of development is tantamount to killing humans.

In addition, another group of US scientists says it has derived embryonic stem cells in mice using an approach that, if scaled to humans, would avoid the need for women to donate unfertilized eggs to produce large numbers of embryonic stem-cells for research. Instead, researchers could use non-viable embryos that fertility clinics and their patients would have disposed of anyway.

Next challenge: Applying this to humans

At this stage, the mouse-cell breakthrough is a proof of concept, researchers caution.

"The real challenge is translating this to human cells, which seem far more resistant" to the kind of manipulation scientists used, notes Clive Svendsen, a stem-cell researcher at the University of Wisconsin's Waisman Center in Madison, Wis. Still, he adds, "it is truly amazing that they can produce cells that look like embryonic stem cells."

For biomedical researchers, understanding how embryonic stem cells transform themselves into all of the various cell types found in an adult human is vital to understanding human development and the problems that can arise during that process. Moreover, if scientists can learn to "steer" stem cells to develop into adult cells of their choosing, they say new therapies might emerge to regenerate diseased or aging tissue.

Many researchers say that progress in the US has been hampered by limits President Bush imposed on federally funded human embryonic stem-cell research nearly six years ago. The limits have prompted several states to set up funding agencies to pay for embryonic stem-cell research within their borders. And this week, the US House was set to vote on a bill that would erase the president's restrictions altogether.

Yet the limits also have prompted some labs to hunt for alternate ways to derive cells.

The adult-cell-to-stem-cell results built on a study published last year by a team from the University of Kyoto. It showed that by introducing into an adult cell four genes common to that mouse's cells and to embryonic mouse cells, that adult cell would be able to generate other major cell types. But the results were unclear about whether the newly altered cells fully mimicked embryonic stem cells.

They figured that somewhere in the large batch of altered cells, there might be some that mimic embryonic stem cells more fully. And they recognized that out of the four genes they initially introduced, two shut down once an embryo passed the stage where its stem cells begin to differentiate into the body's major cell types. So they devised a way to isolate cells with one of these genes, plus a second critical to stem cells. And they figured out how to identify and isolate the cells in which these two genes were active.

The Japanese group, and two US teams who used the same method for altering the adult cells, ran a series of tests to see how closely these artificial stem cells mimicked embryonic stem cells.

"It was surprising even to us" that the new cells acted like embryonic cells in virtually every way, says Marius Wernig, a researcher at the Whitehead Institute for Biomedical Research in Cambridge, Mass. The results appear in today's issue of Nature and the journal Cell Stem Cell.

Hopes and fears – from both sides

If the approach can be applied to humans, he adds, it could prove far more efficient at providing patient-specific cells for therapies than trying to derive the cells through cloning embryos reprogrammed with a patient's DNA. And it sidesteps the ethical quandaries that surround cloning and the use of human embryos.

He and others point out that while the results are encouraging, they shouldn't be used as a reason for clamping a lid on embryonic stem-cell research. Too little is known about the potential usefulness of adult-derived or embryonic stem cells to close the door to any option yet. Still, for people who view life as beginning at conception, this latest research represents "a very promising direction from the vantage point of ethics," says Father Tadeusz Pacholczyk, with the National Catholic Bioethics Center in Philadelphia.

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