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http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2007/11/20/BAQ8TE1KH.DTL&type=tech
(11-20) 07:50 PST SAN FRANCISCO -- (11-20) 09:00 PST SAN FRANCISCO - Separate teams of scientists on two continents are reporting today that they have transformed ordinary human skin cells into stem cells using a technique pioneered last year in laboratory mice.
Kyoto University researchers in Japan are reporting in an on-line edition of the journal Cell that they produced stem cells from human skin cells that were treated with four genes. The four genes had been used successfully in earlier mice experiments.
The newly made human stem cells subsequently proved their versatility. They morphed into nerve cells and microscopic clumps of human heart tissue that beat rhythmically in a laboratory dish.
A nearly identical study, using a different group of four genes, was carried out successfully by scientists at the University of Wisconsin-Madison, and is also being reported today in an on-line edition of the journal Science.
The ultimate promise of stem cell technology is that these master cells might be coaxed into producing organs and tissues to replace those lost by trauma or degenerative diseases - a potential bounty that led California voters in 2004 to approve a $3 billion bond issue for stem cell research.
Richard Murphy, interim president of the California Institute for Regenerative Medicine, which was created by the initiative to distribute that money, hailed the findings.
"We think this is very exciting," he said. "If this pans out, it will be a great advance."
Much of the current research in California is aimed at developing stem cells from cloned human embryos. The goal is to hollow out a human egg, and then infuse it with the nucleus of an ordinary cell - like one from the skin. The egg produces chemical signals that cause the implanted genes to begin developing a human embryo, from which can be harvested the multi-tasking stem cells.
Until last week, some researchers believed that the process was too complex for primates - the order of mammals that includes monkeys and humans. But Oregon researchers disclosed they had successfully cloned monkey embryos, and produced stem cells from them.
The use of human embryos in lab research stirred opposition from the Roman Catholic Church and the anti-abortion movement, because the embryos are destroyed in the process. Medical ethicists are also concerned about the demand the process creates for harvesting human eggs from women.
Such concerns led President Bush in 2001 to ban the use of federal funds to pay for most research on embryonic stem cells. However, the new technique described today appears to pass muster with the administration.
"It's wonderful news," said Dr. Jim Battey, vice chair of Stem Cell Task Force at the National Institutes of Health in Bethesda. "We would be quite enthusiastic to fund this research in the future."
In this new laboratory trick, four genes that are apparently used by eggs to start the natural embryonic development process are inserted into the skin cells. That causes them to produce a full complement of stem cells.
The Kyoto study was led by Dr. Shinya Yamanaka, who developed the technique in mice last year. Yamanaka is setting up a stem cell lab at the Gladstone Institute of Cardiovascular Disease in San Francisco, a UCSF affiliated research center. Yamanaka had spent several years of trial and error to find gene combinations that would convert the mouse skin cells to stem cells. He was surprised to find that essentially the same four genes worked on human cells.
"The advantage of this method is that we don't have to use eggs or embryos," he said.
A disadvantage is that the stem cells produced so far by his technique are likely to cause cancer. One of the four active genes is known to be carcinogenic, and in subsequent experiments, the method did produce cancer in mice.
Yamanaka's team reported this summer that, when they fused the newly created stem cells with a mouse embryo, they were able to produce living mice carrying the genes originally derived from skin cells. But these cloned mice subsequently developed neck tumors.
This creation of cloned mice raises the prospect that a similar set of laboratory techniques might be used to clone a human being - an act that would be universally condemned by scientists as unethical.
Dr. Bernard Lo, an ethicist at UCSF Medical Center, said that because substantial extra laboratory manipulation of these stem cells would be required to make human cloning possible, the risk remains purely theoretical.
"If it is possible to clone primates, then maybe it is possible to clone human beings. But as human beings, we are able to draw the line," he said. "We don't think it is appropriate under any circumstances to clone a human being."
Father Thomas Berg, executive director of the Westchester Institute, a Catholic ethics think tank in Thornwood, New York, said the new technique described in the two papers is a major advance that passes ethical muster. "This is almost a magical moment," he said. "It is a win-win solution for everyone."
Berg said that such research will allow development of stem cell therapies without destruction of human embryos. "We wanted to see science go forward, but in a way that will respect human life," he said.
Dr. Robert Blelloch, a stem cell researcher at the UCSF Institute for Regeneration Medicine, said research in both embryonic stem cells and the use of these new techniques should continue.
He said that while the cancer-causing genes are problematic, future research will focus on finding ways to shut such genes down. In addition, the ultimate goal will be to find out what proteins those genes are producing, and learn techniques to manufacture those proteins and use them directly to turn skin cells into stem cells.
"The nice thing about this experiment is that it opens the door for many other labs to do it," Blelloch said. "This field is moving fast."
Shoukhrat Mitalapov, the Oregon National Primate Research Center scientist whose cloning of monkey embryos made world headlines last week, said the new findings do not make his work obsolete. Because of the cancer-causing problem, he said, it will be a long time before the Yamanaka technique can be used in humans. The use of embryos - cloned or natural - will remain the "gold standard" for production of stem cells, he said.
Researchers still need to learn the stem cell-making secrets of the egg, Mitalapov said. "The only natural system is the egg. The ultimate goal is to understand how the egg does it."
Scientists turn ordinary skin cells into stem cells
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