Image: Stem cells
Chad A. Cowan / Harvard / HHMI
Human embryonic stem cells are shown stained with antibodies specific to an embryonic antigen in this photo from Harvard University. Researchers fused such stem cells with adult skin cells, resulting in regenerative cells that had chromosomes from both of the DNA donors.
By Alan Boyle Science editor
updated 8/22/2005 7:56:58 PM ET 2005-08-22T23:56:58

Scientists say newly published research confirms the power of a technique for producing regenerative cells by fusing adult cells with pre-existing embryonic stem cells rather than using embryos themselves — a technique that could get around the political impasse now surrounding stem cell research.

However, the researchers behind the report in this week's issue of the journal Science cautioned that it would take years or even a decade to perfect the process. One of them, Harvard researcher Kevin Eggan, voiced strong support for controversial legislation that would allow federal funding for the creation of new stem cell lines from human embryos.

The method pioneered by Eggan and his colleagues at the Harvard Stem Cell Institute involves blending millions of human embryonic stem cells with millions of adult cells in a special chemical brew. Roughly one out of 1,000 of the resulting hybrid cells was "reprogrammed" to act like an embryonic stem cell, with the capacity to differentiate into any of the main types of body cells, ranging from neurons to hair, the researchers said.

If scientists can harness the regenerative power of such cells, they could create tailored cells for use in future therapies — mending severed spinal cords, boosting failing hearts or giving insulin-producing cells to diabetics, for example.

Cell fusion could conceivably be used to mass-produce regenerative cells — but there are still huge hurdles standing in the way, Eggan told reporters during a Monday telephone news briefing. The biggest is that the hybrid cells produced at Harvard contain all the genetic material from the adult cells as well as the stem cells. In order for such cells to be used in therapy, researchers would have to find a way to remove the stem cell DNA without removing the "stemness" of the hybrid cells.

"The cells that we have made and reported will never be useful for therapy or for studying diseases. ... What's important here is the process, the phenomenon, that this indeed can happen," he said. "And now what we're going to do is go to work on the nuts and bolts of this process."

Eggan's findings don't come as a surprise: In the weeks since he presented them at a San Francisco stem-cell conference, they have been reported by various news outlets, including . For that reason, Science released the paper for distribution on Sunday night without the usual embargo restrictions.

Nevertheless, the fact that the findings were finally published in Science, one of the world's most prestigious research journals, gave a boost to the field of cell reprogramming, which seeks to extend the magic of stem cells to any patient's ordinary cells.

"It's very positive," Dr. Yuri Verlinsky, another cell-fusion pioneer at Chicago's Reproductive Genetics Institute, told "Somebody else is trying to do what we are doing."

Sizing up the research teams
Eggan, Verlinsky and Australian researcher Alan Trounson are among the scientists who already have reported advances in cell reprogramming. Eggan told that the main significance of his group's research was to lay a solid foundation for other studies in the field.

"If anything, our experiments are a precursor to theirs," Eggan said of the other efforts.

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Verlinsky, meanwhile, said that his technique — which involves spinning the nucleus out of a stem cell and replacing it with an adult cell's nucleus — avoids Eggan's problem of having too much DNA remaining in the cell. He said a paper based on his research was being considered for future publication.

"We are on the right track," Verlinsky said. "We are ahead of them."

In the Science paper, Eggan and his colleagues painstakingly outline how they used two types of antibiotic-resistant genes to winnow out hybrid cells with the properties of stem cells, and how they verified that the cells contained the chromosomes from both donor cells, 92 in all. They started by fusing skin cells with an embryonic stem cell line that had been created at Harvard without federal funding. Then they confirmed their results by fusing bone cells with an older human stem cell line that was approved for federally funded research.

Those procedures demonstrated that the research could be conducted even under current federal funding guidelines.

Progress and politics
The Harvard researchers wrote that the technique "may circumvent some of the logistical and societal concerns" surrounding stem cell research in the United States.

Just last month, Senate Majority Leader Bill Frist, R-Tenn., announced that he would go against President Bush's wishes and vote for a bill already approved in the House that would lift some of the limits on federal funding for new stem cell lines derived from human embryos.

Even if that bill passes the Senate, sometime after the current summer recess, it would still face a veto threat from the White House. Yet another bill would support funding for cell reprogramming and other alternative research avenues, and if that legislation comes up for a vote, it would likely pass with little controversy.

Eggan said that the research into cell reprogramming should not be used to throw up political roadblocks to other stem cell research that might yield new therapies more quickly. "I strongly, strongly support the derivation of new lines," Eggan said, "and I'm very hopeful that the Senate version of the House ... bill will pass when the Senate is back in session."

The road ahead
Going forward, some researchers will try using cell fusion to figure out a chemical mechanism for switching adult cells into a stem cell-like mode, Eggan said, while others will try to blend adult cells with components from stem cells to regenerate tissue.

Another member of the Harvard research team, Douglas Melton, emphasized in a written statement that reprogramming could not yet take the place of somatic-cell nuclear transfer, or "therapeutic cloning," which uses precious human eggs to create new embryos from which stem cells are harvested.

"Taking advantage of this current capability — such as colleagues in South Korea and other countries are doing — is critical if we are to maintain the progress necessary to realize the extraordinary clinical potential of this technology,” Melton said.

But if the reprogramming process can be perfected, it would offer advantages over therapeutic cloning, Eggan said.

“We can make a lot of embryonic stem cells, and we can genetically manipulate embryonic stem cells, which to a biologist is really exciting, because now we can get there and we have a system which is manipulatable in different ways than cloning is. It's going to let us have an alternative to eggs as a source of material to look at," he said. "This is really cool."

In addition to Eggan and Melton, the Harvard research team included Chad Cowan and Jocelyn Atienza. The study was supported by the Howard Hughes Medical Institute.

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