Scientists replicate stem cells

A technique that coaxes adult skin cells into acting like embryonic stem cells could remake the ethical landscape

Researchers from Japan and Wisconsin reported Tuesday that they had reprogrammed mature human cells to behave almost exactly like embryonic stem cells, a biological breakthrough that recasts the field's ethical, scientific and economic landscape.

By activating a handful of dormant genes, the researchers were able to coax the cells back to a point in embryonic development before they had committed to becoming a particular type of tissue.

The rejuvenated cells were able to grow into all the body's main tissue types, including muscle, gut, cartilage, neurons and heart cells.

The discovery provides a clear road map for creating genetically matched replacement cells that could be used to treat patients for a variety of diseases -- the personalized biological repair kits that are the ultimate goal of regenerative medicine.

For scientists, the method offers an alternative to the tricky and still unsuccessful cloning process in which a patient's DNA is inserted into a human egg to create a cloned embryo whose stem cells theoretically could be harvested.

The technique also bypasses the debate over the morality of destroying embryos in the cause of alleviating human suffering.

"It's a win-win," said Richard Doerflinger, secretariat for pro-life activities at the U.S. Conference of Catholic Bishops in Washington.

"The scientists can get all the benefits they think they might get from embryonic stem cells, and the rest of us can applaud and support it."

Glitches need solving

Several key hurdles remain before the technique is ready for clinical use. The viruses employed to turn on the genes cause mutations that can lead to cancer, and one of the genes itself has a tendency to cause tumors.

Scientists said solutions to these problems are in the works.

"This is a tremendous scientific milestone -- the biological equivalent of the Wright brothers' first airplane," said Dr. Robert Lanza, a stem-cell researcher at Advanced Cell Technology in Worcester, Mass., who wasn't involved in the research.

The White House praised the work as an example of cutting-edge research that was conducted "within ethical boundaries."

"The president believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life," press secretary Dana Perino said.

Stem cells are coveted for their ability to grow into any kind of cell, such as the insulin-secreting islet cells that diabetics need or brain tissue that could treat stroke victims.

Until now, the only source of such "pluripotent" cells was the inner cell mass of an early-stage embryo, and harvesting them required the destruction of the embryo.

Flipping genetic switch

The key advance was made by Dr. Shinya Yamanaka and his colleagues at Kyoto University, who spearheaded the reprogramming technique in mice. They dubbed their cells induced pluripotent stem cells, or iPS cells.

In their new study, published in the journal Cell, they used human cells taken from the subsurface layer of facial skin belonging to a 36-year-old woman.

The idea was to turn on genes that are active during embryonic development to see if they would rewind mature adult cells. After testing combinations of 24 candidate genes, they hit upon a group of four.

Yamanaka's group used a retrovirus to turn on the genes. The proteins, known as transcription factors, initiated a still-unknown biochemical process that returned the cells to an embryonic state.

A second group of researchers, led by Dr. James Thomson at the University of Wisconsin in Madison, were able to use proteins to reprogram fetal connective tissue cells called fibroblasts. The technique also worked on fibroblasts from the foreskin of newborn boys. Their results were published in the journal Science.

Thomson, who isolated the first human embryonic stem cells in 1998, said that the technique was being tested in older cells and that he was optimistic it would work.

Both the new discoveries will bring a host of practical benefits.

President Bush made most embryonic stem-cell research off-limits for federal funding, but this line of work is eligible because it doesn't destroy human embryos. Indeed, Thomson's study was funded in part by the National Institutes of Health.

Parents after death?

Although the new technique dodges some significant ethical problems, it also creates new ones, said Insoo Hyun, a bioethicist at Case Western Reserve University in Cleveland.

In previous experiments, mouse iPS cells were transformed into sperm and egg cells. If the same could be done in people, he said, "it transforms what we think about human fertility."

Theoretically, the method would allow people to reproduce even after death if they banked a tissue sample.

"A person doesn't even have to be alive to create sperm or eggs," Hyun said. "It really is a new technology that brings with it a new set of issues."