Stem Cell Research - Looks Promising!

From the Wall Street Journal


Advance in Stem Cells Avoids Ethical Tangles
By GAUTAM NAIKNovember 20, 2007 7:36 p.m.

The promise of using cells from human embryos to treat disease has moved a tantalizing step closer to reality – but without the ethical shackles that have long hindered its progress. The breakthrough is likely to bolster the cause of those who oppose embryo research, and accelerate the pace of stem cell research as scientists rush to build on the new approach.

In a compelling scientific feat, independent teams of researchers in Japan and the U.S. created human embryonic stem cells without destroying any human embryos. The technique appears to be easier, cheaper, and more ethically appealing than an alternative approach that involves a controversial form of human cloning.

Scientists said they "reprogrammed" mature human cells in such a way that they reverted to a primordial, embryonic-like state in a laboratory dish. The hope is to some day convert those cells into fresh heart, nerve or other tissue and transplant them into patients to treat diabetes, Parkinson's and other ailments.

The achievement won accolades from Catholic groups and leading scientists. "I suspect this will completely supplant the need to use [cloning techniques] to achieve tissue regeneration," says Sir Martin Evans, a British stem-cell pioneer who shared this year's Nobel Prize for Medicine. "We've all been waiting for this."

Ian Wilmut, who famously got the ball rolling a decade ago by cloning Dolly the sheep, is so impressed that he plans to abandon cloning experiments altogether. In his quest to find new treatments for motor neuron disease, he's now betting on the newer, reprogramming approach. "Cloning has had its impact," says Prof. Wilmut. "It seems we should all focus our efforts on reprogramming."

Still, many scientists want reprogramming techniques to be pursued alongside more embryo-based stem cell research. But in Washington, where stem cell research has long been the subject of bitter disputes, the new findings are certain to galvanize policymakers who believe it is immoral to destroy human embryos for research.

Since 2001, the Bush administration has decreed that federal funds may only be used to pay for research using roughly 60 or so stem-cell lines obtained from human embryos that existed at that time. Many Bush supporters – especially those on the religious right – would like that constraint to remain, and possibly even be tightened.

One set of experiments, published Tuesday in the journal Cell, was led by Shinya Yamanaka of Kyoto University, a pioneer in the reprogramming field. A second paper was published in Science by researchers at the lab of James Thomson of the University of Wisconsin, who isolated the first human stem-cell line in 1998.

In both cases, the scientists inserted several genes into a mature human cell. For reasons that no one can yet fully explain, this reset the molecular clock and turned older, mature cells into embryonic-like cells. Even among researchers, the result has a touch of science-fiction.
"You have this extremely strong arrow of time -- and it's going completely backwards," said Dr. Thomson. (my emphasis)

Douglas Melton, co-director of the Harvard Stem Cell Institute says: "You have to give Yamanaka enormous credit. Most people, including me, wouldn't have thought about using this approach."

But reprogramming has plenty of hurdles to overcome before it can yield useful medical treatments. To ferry the genes into the cells, both teams had to use dangerous viruses as a transport mechanism. Unfortunately, the DNA of those viruses gets incorporated into the genetic structure of the cells, causing cancer or other unwanted side-effects. Dr. Yamanaka and others are now racing to find a virus that doesn't trigger those problems.

The most famous reprogramming experiment was the cloning of Dolly the sheep, in 1996. However, in that case, a sheep's egg mysteriously reprogrammed a mature sheep's cell and returned it to an embryonic state known as a blastocyst. When that cloned blastocyst was carried to term, it yielded Dolly.

Some researchers then began to wonder whether it would be possible to avoid eggs and reprogram a cell by introducing genes. In a paper published in 2006, Dr. Yamanaka and a colleague showed how four specific genes could do exactly that in a mouse cell. But the fresh mouse cells failed to be successfully incorporated into mouse embryos – a vital test.
Then, in June 2007, Dr. Yamanaka and two other independent teams of researchers published another set of studies showing that they had surmounted the earlier problem. Each team used the same four genes to reprogram a mouse cell and return it to its youthful, embryonic stage. When implanted into embryos, the cells produced healthy mice.

That result set off a global race among scientists seeking to replicate the mouse results with human cells. But almost nobody predicted that the human barrier would fall quite so quickly.
"We were very surprised because human and mouse embryonic cells are very different," says Dr. Yamanaka, who is also a senior investigator at the Gladstone Institute of Cardiovascular Disease in San Francisco.

Dr. Yamanaka's discoveries have sparked a flurry of fresh research. Some scientists are introducing different kinds of genes, in the hope of improving the reprogramming process. Dr. Melton says his colleagues want to see if they can pull off the same trick by using chemicals instead of genes.

Unlike cloning, "the wonderful thing about this approach is that it's easy. You're going to see lots and lots of labs give it a try," predicts Robert Blelloch, a stem cell biologist at the University of California, San Francisco, who recently published his own reprogramming experiments partly based on Dr. Yamanaka's breakthroughs.

However, the nuclear transfer approach – which uses a cloning step to get embryonic stem cells – isn't likely to disappear. Just last week, researchers in Oregon used the technique to create embryonic clones of monkeys.

Of course, trying nuclear transfer with human cells is harder. Human eggs are in short supply; the technology is tricky and expensive; and funding isn't so readily available. A major scandal has hurt, too. In 2005, a Korean researcher published a study that appeared to show how he'd used the approach to create human-embryonic clones. The claim turned out to be fraudulent.
By contrast, "any scientist with basic technology in molecular and cell biology can do reprogramming," says Dr. Yamanaka. "If we can overcome the issue [of using dangerous viruses to ferry the genes into cells], many more people will move from nuclear transfer to this method."