In a dramatic advance for therapeutic cloning, South Korean researchers have established 11 new human embryonic stem cell lines by taking genetic material from the skin cells of injured or sick volunteers and inserting it into donor eggs.
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The advance means that patients with some disorders could some day be treated with genetically matched replacement cells, avoiding immune system rejection. The study volunteers had a variety of conditions, including spinal cord injury, diabetes and genetic immune system deficiency.
"This research is a giant step forward toward conquering devastating diseases," said lead investigator Dr. Woo Suk Hwang, of Seoul National University, during a recent visit to Pittsburgh.
His team got a helping hand from Gerald Schatten, director of the Pittsburgh Development Center at Magee-Womens Research Institute. Schatten assisted with analysis, interpretation and preparation of the data for publication today in the journal Science.
The researchers said the experiments were conducted to explore the therapeutic value of embryonic stem cells, not to clone a human being.
Also, "it's important to remember there is a long, long journey from the laboratory bench ... to the safe and responsible transplantation investigations," Schatten said.
The South Korean team extracted the genetic material from an unfertilized egg and replaced it with the DNA-containing nucleus of a skin cell. With a little scientific encouragement, the altered egg grew, as an embryo would. However, its growth halted at a very early stage when the scientists removed its stem cells for culture.
Embryonic stem cell lines were established from male and female skin cell donors who ranged in age from 2 to 56. In all but one case, they were not related to the egg donors, who were not paid for their contributions. For one line, a female patient's genetic material was inserted into her own egg.
"Last year, we established one cloned embryonic stem cell line from 242 eggs from 16 women donors," Hwang said. "Our recent outcomes revealed 11 embryonic stem cell lines from 185 eggs from 18 donors."
That's a 15-fold improvement in efficiency, he said. Also, the researchers used human rather than mouse feeder cells to provide nutrients for the stem cell lines, lessening concerns about contamination.
The high success rate is impressive, said John Gearhart, director of the stem cell program at Johns Hopkins University's medical school. Naysayers predicted that establishing an embryonic stem cell line through cloning techniques would require hundreds of women to donate multiple eggs.
With the South Korean results, Gearhart said. "you could almost argue it would take essentially one cycle of a hormone regimen on a young woman to generate enough oocytes [eggs] that you could generate a cell line for somebody."
Ian Wilmut, the Scottish researcher who led the team that cloned Dolly the sheep, congratulated the South Korean researchers.
"These new observations make a very significant step forward," he said in a statement issued by his office. "We can now look forward confidently to the use of cells from cloned human embryos for research."
Wilmut's team was recently awarded a license from U.K. authorities to use cloning techniques to study the neurologic disorder amyotrophic lateral sclerosis, also known as Lou Gehrig's disease. It plans to collaborate with Hwang's group to efficiently produce embryonic stem cells for the project.
Schatten is attempting to replicate and possibly expand upon the South Korean work in nonhuman primates. He said he probably won't work with the human cell lines because he'd only be able to do so in a privately funded lab.
The Bush administration has limited federal funding for embryonic stem cell research to a few already established lines and has considered banning any form of human cloning. Pennsylvania doesn't permit the creation of new stem cell lines.
Within the next week, a closely divided U.S. House is expected to vote on legislation that would, for the first time, loosen the restrictions that Bush imposed on federal funding for the field in 2001, the Washington Post reported.
That legislation would not allow funding of cloning research like that done in Korea -- a kind of research the House has twice voted to ban and which the Senate has deadlocked over for years. Rather, it would facilitate the less contentious use of frozen embryos about to be discarded by fertility clinics, the Post said.
Embryonic stem cells have the potential to create supplies of specialized cells that scientists say might be able to treat Parkinson's disease and other conditions.
The next hurdle is to learn how to guide the stem cells into generating other cell types, such as neurons and muscle cells.
"We've got to convert these cells into the kinds of cells that are needed in these diseases and injuries," Gearhart said. "It's certainly going to be a while before we would expect these to be going into the clinic."
Hwang's group wants to establish more embryonic lines and is studying the stem cells in animal experiments of spinal cord injury.
The South Korean techniques also can help scientists produce other stem cell lines with specific gene alterations, perhaps allowing them to ferret out disease mechanisms at a cellular level, Schatten said.
Because they'd be working with human cells, "not only will the science move faster, it will move more accurately," he said.
Hwang's team caused an international stir last year when it derived stem cells from a cloned human embryo for the first time. Many experts, including Schatten, said their work could indicate to unscrupulous researchers that reproductive cloning is feasible.
That might be even more true in light of their latest research, but the South Korean researchers assert that their work is strictly to explore therapeutic avenues.
"Cloning is not our proposal," Hwang said. "Our research purpose is to find the method and technology for curing devastating diseases."
Schatten added, "Human reproductive cloning is unsafe, it's unethical and, just like in the Republic of Korea, it ought to be illegal everywhere. There's nothing about this that involves reproductive cloning."
Even if a scientist tried implanting a cloned embryo in a woman's uterus, it's extremely unlikely that a viable pregnancy or birth would result, the experts say. Schatten has attempted this many times in monkeys without success.