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Stem cell milestone achieved

Scientists coax mature human cells to behave like embryonic ones, a step that may bridge the ethical divide.

November 21, 2007|By Karen Kaplan | Los Angeles Times Staff Writer

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 instantly 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 in time 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 main tissue types in the body, 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 a straightforward 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 thorny 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."

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 also has a tendency to cause tumors.

But scientists said solutions to these problems were 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.

The discovery has been eagerly anticipated since June, when three research groups achieved the same feat in mice. Scientists expected the experiments to be repeated in humans, but many said it would take years, not months.

Stem cells are coveted for their ability to grow into any kind of cell, such as insulin-secreting islet cells that diabetes patients 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 the only way to harvest them was by destroying the embryo.

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

In their new study, published in the journal Cell, they applied essentially the same recipe used with the mice skin cells to 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 whether they would rewind mature adult cells. After testing combinations of 24 candidate genes, the team hit upon a group of four that produces the proteins Oct4, Sox2, c-Myc and Klf4.

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.

The researchers grew the iPS cells in dishes and found they behaved almost exactly like embryonic stem cells. Under the right conditions, they became neural cells, or cardiac cells that beat in unison. When injected into mice, the iPS cells formed tumors containing a jumble of body parts.

"They are very, very close, if not functionally identical to human embryonic stem cells," said Owen Witte, director of the Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Altogether, the researchers were able to create about 10 lines of iPS cells from each batch of 50,000 skin cells.

"The incredible thing about it is how easy it seems to be," Doerflinger said. "From one little biopsy of a skin sample, you always get enough cells changing to create a stem cell line."

Yamanaka said he could not use human embryonic stem cells in Japan, so he hadn't been able to make a head-to-head comparison between those cells and the new iPS cells. He said he intended to do the tests at UC San Francisco's Gladstone Institute of Cardiovascular Disease.

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