Skin Cells Converted to Stem Cells
Monday, August 22, 2005; 11:30 AM
Scientists for the first time have turned ordinary skin cells into what appear to be embryonic stem cells -- without having to use human eggs or make new human embryos in the process, as has always been required in the past, a Harvard research team announced yesterday.
The technique uses laboratory-grown human embryonic stem cells -- such as the ones that President Bush has already approved for use by federally funded researchers -- to "reprogram" the genes in a person's skin cell, turning that skin cell into an embryonic stem cell itself.
The approach -- details of which are to be published this week in the journal Science but were made public on the journal's Web site yesterday -- is still in an early stage of development.
Researcher Kevin Eggan speaking with reporters on Monday said, "I can't stress enough that this technology is not ready for prime time right now. It is not a replacement for those techniques that we already have for derivation of embryonic stem cells," the Associated Press reported.
"There are lots of stumbling blocks still ahead," said B.D. Colen, a spokesman for Harvard.
But if further studies confirm its usefulness, the technique could offer an end run around the heated social and religious debate that has for years overshadowed the field of human embryonic stem cell research.
Since the new stem cells in this technique are essentially rejuvenated versions of a person's own skin cells, the DNA in those new stem cells matches the DNA of the person who provided the skin cells. In theory at least, that means that any tissues grown from those newly minted stem cells could be transplanted into the person to treat a disease without much risk that they would be rejected, because they would constitute an exact genetic match.
Until now, the only way to turn a person's ordinary cell into a "personalized" stem cell such as this was to turn that ordinary cell into an embryo first and later destroy the embryo to retrieve the new stem cells growing inside -- a process widely known as "therapeutic cloning."
That prospect, like others in the promising arena of human embryonic stem cell research, has stirred strong emotions among those who believe that days-old human embryos should not be intentionally destroyed.
Embryonic stem cells are capable of becoming virtually any kind of cell or tissue and are being intensely studied around the world as the core of a newly emerging field of regenerative medicine, in which researchers hope to grow new tissues to revitalize ailing organs. Although human embryonic stem cells have never been tested in humans, some researchers expect human clinical trials to begin within a year or so. Researchers caution, however, that like many other nascent therapies that initially seemed promising, stem cells may never live up to their promise.
If some lingering, and potentially daunting, uncertainties can be dealt with successfully, the new technique "may circumvent some of the logistical and societal concerns" that have hampered much of the research in this country, Chad A. Cowan, Kevin Eggan and colleagues from the Harvard Stem Cell Institute report in the Science article.
More immediately, the new work could have an impact on Capitol Hill, where the Senate is poised to vote on legislation -- already passed by the House -- that would loosen Bush's restrictions on human embryonic research.
Last month, Senate Majority Leader Bill Frist (R-Tenn.) surprised many of his colleagues by announcing he would break with the president and support the Senate bill, which Bush has promised to veto.
Some opponents of relaxing the current restrictions have argued that new techniques will soon eliminate the need to use human eggs or embryos to make cells that are, for all intents and purposes, human embryonic stem cells. They and others have for some months predicted that if such new findings were to emerge, they could shift the balance of votes in the Senate.
The researchers emphasize in their report that the technique is still far from finding an application in medicine. Most important, they note: Because it involves the fusion of a stem cell and a person's ordinary skin cell, the process leads to the creation of a hybrid cell. While that cell has all the characteristics of a new embryonic stem cell, it contains the DNA of the person who donated the skin cell and also the DNA that was in the initial embryonic stem cell.
At some point before these hybrid cells are coaxed to grow into replacement parts to be transplanted into a person, that extra DNA must be extracted, the researchers write.
The team describes this task as a "substantial technical barrier" to the clinical use of stem cells made by the new technique.
They do not mention that several teams, including ones in Illinois and Australia, have said in recent interviews that they are making progress removing stem cell DNA from such hybrid cells. None of those teams has published details of their results. But several leading researchers have said they believe it will be feasible to remove the extra DNA.
Some even suspect that the new technique for making personalized stem cells would still work even if the "starter" stem cells' DNA were removed before those cells were fused to the skin cells. It is not clear whether the genetic reprogramming imposed upon the skin cells by the fused stem cells requires the initial presence of the stem cells' DNA, or whether fluids in the initial stem cells can do the job themselves.
"Their data are certainly very good . . . and quite significant," said John Gearhart, a stem cell researcher at Johns Hopkins Medical Institutions. But the extra DNA "is problematic."
"I think we have to keep our eye on the ball here," Gearhart said. "If this stuff proves to work, that's wonderful. But we're just not there yet, and it's going to take a long time to demonstrate that. Meanwhile, other techniques already work well. So let's get on with it."
Still, it is fascinating, Gearhart said, to see such good evidence that something in embryonic stem cells is able to turn an ordinary skin cell into the equivalent of an embryonic stem cell -- a genetic alchemy apparently accomplished by turning key genes in the skin cell either "on" or "off."
Even if the work does not lead directly to clinical applications, he and the Harvard researchers said, it is likely to boost the amount and quality of research into what stem cells really are and how they work.