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Science.com

October 29, 2005



Breakthrough: Stem cells for the world



By Karen Kaplan


The South Korean researcher who was the first to clone human embryos for the creation of stem cells has established a worldwide stem cell bank to make the technology available to other scientists.

The World Stem Cell Foundation, unveiled recently in Seoul, intends to produce about 100 new cell lines each year and make them available to scientists, particularly those in the US who have been stymied in their research by federal funding restrictions.

The creation of the stem cell bank offers the possibility of sidestepping the Bush administration’s restrictive policies governing the use of human embryos for research purposes.

“I think US scientists will be lining up to request them,” said Dr George Q. Daley, a professor of biological chemistry and molecular pharmacology at Harvard Medical School.

The foundation is based at Seoul National University and led by Woo Suk Hwang, a professor at the school’s College of Veterinary Medicine. Satellite labs will be established in San Francisco and Oxford, England.

So far, Hwang’s lab is the only one that has been able to master the delicate procedure of removing DNA from human eggs, replacing it with DNA from sick patients, and coaxing the eggs to develop to the point where stem cells can be harvested.

Researchers will be able to apply to have stem cells created from the DNA of their choice; once developed, the cell lines will be made available for other scientists to use as well.

The foundation’s organizers declined to discuss their plans before their news conference in Seoul. Details were provided by scientists who had been briefed on the plan and by a report that was to be published online by the New England Journal of Medicine to coincide with the announcement.


The World Stem Cell Foundation intends to produce about 100 new cell lines each year and make them available to scientists


The procedure offered by the South Koreans — called somatic cell nuclear transfer, or therapeutic cloning — is essential for creating stem cells tailored to individuals. It is a key step towards developing medical cures based on stem cells, which have the ability to become virtually any cell in the body. For example, such cells could be used to treat juvenile diabetes by growing replacements for faulty islet cells that fail to make insulin.

Scientists in the US and other countries have been trying to replicate Hwang’s achievement, so far without success. Some US scientists said they were convinced that such work would be occurring in the US if the government hadn’t limited the use of federal funds for embryonic stem cell research.

“There’s no doubt that the federal policy has chilled research in this area,” said Dr Arnold Kriegstein, director of the Institute for Stem Cell and Tissue Biology at UC San Francisco. “How could it be otherwise if there are threats from the floor of Congress that this procedure might be criminalized?”

The South Korean stem cells could be used in all states except South Dakota, which specifically prohibits the importation of human embryonic stem cell lines, said LeRoy Walters, a senior research scholar at Georgetown University’s Kennedy Institute of Ethics, who tracks state laws involving stem cells.

But some scientists said they would not be comfortable working closely with the foundation until it committed itself to ethical guidelines regarding the use of human embryos and the eggs needed to create them.

Hwang’s group has pledged not to patent new cell lines, but it does plan to charge fees to recoup costs. In the US, it is customary to charge academic researchers up to $5,000 for a stem cell line, though many institutions give them away free.

The South Korean government will pay for the foundation’s work in Seoul, and private parties will be asked to subsidize operations in San Francisco.

The San Francisco lab could be eligible to apply for funding from the California Institute for Regenerative Medicine, the $3-billion state agency established by Proposition 71 to fund stem cell research.

Zach Hall, agency president, said he was eager for California scientists to collaborate with the South Koreans and benefit from their expertise. But when Hwang visited last month to discuss a partnership, Hall demurred.

“We just don’t know enough about how it will actually operate for us to have a formal relationship with them,” he said.

Meanwhile, scientists say they have created viable embryonic stem cell lines without destroying any embryos — a development that could clear ethical barriers that have sharply restricted federal funding for the controversial research.

Two separate techniques were demonstrated in mice, and researchers are optimistic the processes could be replicated with human cells. The new methods were published online by the journal Nature.

Scientists and ethicists said the approaches offered a potential compromise with social conservatives who see embryonic stem cell research as an untenable trade-off that amounts to destroying life to create medical cures.

Dr William B. Hurlbut, a member of the President’s Council on Bioethics, said he had persuaded several religious and conservative philosophers that at least one of the new approaches was morally sound. But given the intractable debate about when life begins, there are lingering ethical concerns.

Neither method “really quells the ethical debate,” said Dr George Q. Daley, a professor of biological chemistry and molecular pharmacology at Harvard Medical School. “It’s not clear it’s going to answer all the critics.”

Protection of human embryos has been the guiding principle behind President Bush’s stem cell funding policy. Bush was the first to approve federal money for the research, but he limited funding to the cell lines already in existence in 2001 to avoid having taxpayers subsidize the destruction of embryos. Scientists have said that only about 20 of them were usable.

Those lines, which have proven unsuitable for some research, were derived from frozen embryos donated by couples that no longer needed them for in vitro fertilization. The federal restrictions have hampered scientists seeking to tap the therapeutic potential of embryonic stem cells, which have the capacity to grow into any cell type in the human body. Researchers believe, for example, that the cells might eventually be used to treat juvenile diabetes by growing replacements for faulty islet cells that make insulin.

Some researchers have moved forward by using private funds to create their own lines of embryonic stem cells. California has taken the most aggressive position, passing Proposition 71 in 2004 to provide $3 billion for stem cell research.

One of the new approaches reported in Nature is based on a routine procedure used by fertility clinics to look for genetic defects in embryos.

Dr Robert Lanza, medical director of Advanced Cell Technology Inc. in Worcester, Massachusetts, and an author of one of the papers, extracted a single cell from a mouse embryo that developed in the laboratory into an eight-cell bundle.

After removing the cell, called a blastomere, Lanza’s team surrounded it with human embryonic stem cells from the Bush-approved lines, allowing the mouse cell to pick up the appropriate biochemical cues to start behaving like a stem cell.

Using 125 blastomeres, they were able to create five cell lines that tests found had the same properties as embryonic stem cells. To demonstrate that the single-cell biopsy posed minimal risk to the embryo, seven-cell mouse embryos were implanted into surrogate mothers. They resulted in live births 49 per cent of the time, virtually the same as for the regular eight-cell embryos.

Lanza said human stem cell lines could be created using single cells extracted for genetic diagnosis at in vitro fertilization clinics.

In a laboratory dish, the extracted cell would be allowed to divide into two. One cell could be screened for genetic defects and the other used to create stem cells, he said.

“It’s relatively simple,” Lanza said. “It does not damage the embryo, and it’s been used on thousands of healthy babies.” The other approach, developed by MIT biologist Rudolph Jaenisch, relies on deactivating a gene needed to implant an embryo into a uterus. — Dawn/LAT-WP News Service (c) Los Angeles Times



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