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Stem cell breakthrough could avoid ethical concerns

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Advocates on both sides of the ethically charged debate over human embryonic stem cells hailed two breakthrough studies unveiled Tuesday that suggested simple human skin cells might one day lead to a vast array of new treatments without destroying embryos.

Until now, researchers hoping to use stem cells to create replacement organs and medicines for numerous diseases had assumed their best hope was with human embryonic stem cells, which have the flexibility to turn into any tissue type.

But the studies published in the journals, Cell and Science indicate that other cells plucked from a person’s hand or face may be just as useful.

One study was headed by Shinya Yamanaka of Japan’s Kyoto University, who opened a laboratory at San Francisco’s J. David Gladstone Institutes this summer. In a feat since duplicated by other scientists, Yamanaka drew acclaim last year by reprogramming mouse skin cells back to a state similar to embryonic stem cells.

Now, a Kyoto team led by Yamanaka and Wisconsin scientists including stem-cell pioneer James Thomson have done the same thing with human skin cells.

Although both teams cautioned that more studies are needed to perfect the procedure, other experts proclaimed the accomplishments as a promising way to avoid the ethical debate surrounding human embryonic stem cells, which come from 4- to 5-day-old discarded embryos.

“This is a tremendous scientific milestone – the biological equivalent of the Wright Brothers first airplane,” said Dr. Robert Lanza, chief scientific officer for Advanced Cell Technology of Alameda. “It’s a bit like learning how to turn lead into gold.”

George Daley, president of the International Society for Stem Cell Research, the studies “hugely significant.”

Susan Fisher, a stem-cell researcher at University of California San Francisco, said she was impressed at how quickly the art of reprogramming cells is progressing.

“I think a lot of people thought there would be a lot of hang time between the work in the mouse and the work in the human,” she said.

Critics of studies with human embryonic stem cells also endorsed the reprogramming.

The White House issued a statement saying, “President Bush is very pleased to see the important advances in ethical stem cell research reported in scientific journals today. . . .The President believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life.”

Tony Perkins of the Washington-based Family Research Council called the studies historic. “This demonstrates what pro-lifers have been saying since the beginning,” he said. “It is never necessary to compromise ethics by destroying life in order to achieve scientific aims.”

Richard Murphy, interim president of the $3 billion California Institute for Regenerative Medicine said “these are very exciting new directions for stem-cell research.”

Since voters created it in 2004, the institute’s focus has been on human embryonic stem cell studies, because Bush had restricted federal financing for that kind of research. But now that scientists can give skin cells properties similar to human embryonic stem cells, “we think that we need to have parallel tracks,” with some studies on embryonic stem cells and others on reprogramming, Murphy said.

The institute already has given a few grants to scientists attempting to reprogram cells and Murphy said it intends to seek applications for more in the spring.

Because human embryonic stem cells can develop into more than 200 tissue types in the body, many scientists envision them one day being used in laboratories to grow muscles, nerves and even whole organs, which could then be implanted into sick people.

Another potential application is to use the cells to create tissues afflicted by diseases, which can be tested with drugs to see which medicines heal the tissues. Scientists believe the same technique could be used on stem-cell grown tissues bearing the genes of different people, to make treatments tailored to specific groups or individuals.

However, many people abhor research with embryonic stem cells, because they believe it destroys human life. Consequently, scientists have been laboring to create cells with embryonic-like properties that aren’t derived from embryos.

In a study last year, Lanza claimed to have made human embryonic stem cell colonies by extracting a single cell from an embryo in a way that would allow the embryo to keep growing. Reprogramming cells is a different strategy to achieve the same end.

Yamanaka and the Wisconsin team that involved Thomson, the first to coax stem cells from human embryos in 1998, emphasized that more study is needed to determine if their reprogrammed cells are precisely like human embryonic stem cells.

Scientists long have suspected that human embryonic stem cells contain a few key genes that give the cells “pluripotency,” the ability to become every tissue type. Through tests, the teams each picked four genes that seemed crucial to this capability.

Then they added the genes to the skin cells along with a retrovirus, which can insert genetic material into a cell’s DNA. After a couple of weeks, the cells became pluripotent.

“Nobody has any idea the exact mechanism why these genes can actually turn skin cells back to human embryonic stem cells states,” said Junying Yu, who led the Wisconsin team. But she suspects the genes turn on genetic material within the cells that helps revert the cells to an embryonic state.

Yu added that the transformed skin cells were injected into mice where they developed into a variety of tissue types, indicating the cells had acquired embryonic stem-cell properties.

The teams’ reprogramming techniques will have to be modified to safely be used for treatments. One of the four genes Yamanaka’s group used, the c-myc gene, can cause tumors. The Wisconsin team avoided that problem by not using the gene. However, both teams also relied on retroviruses to implant the genes into the skin cells, and retroviruses can cause cancer, too.

“Retroviral vectors have a messy and dangerous history,” said Christopher Thomas Scott, executive director of Stanford’s Program on Stem Cells in Society.

In 2002, a Paris study with an experimental gene-based treatment that involved a retrovirus added to stem cells was halted after four infants developed cancer and one died.

However, it may be possible to insert the genes without retroviruses, by perhaps using an agent that doesn’t linger in the cells long enough to cause cancer, said Renee Reijo Pera, director of Stanford’s Center for Human Embryonic Stem Cell Research and Education. And she cheered the studies.

“I’m completely impressed,” she said. “This really accelerates our field.”

By Steve Johnson
Mercury News

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