HARVARD GAZETTE ARCHIVES
Adult cells transformed into stem cells
Genetic clock rewound
By William Cromie
Harvard News Office
A new type of hybrid cell created at Harvard University could eventually solve the mystery of how embryonic stem cells develop into specialized adult cells, and provide genetically tailored treatments for many human diseases.
What's more, the technique holds out the possibility of doing this without creating or destroying human embryos.
The researchers fused adult skin cells with embryonic stem cells in such a way that the genes of the embryonic cells reset the genetic clock of the adult cells, turning them back to their embryonic form.
Such adult-cum-embryo cells, taken from people with juvenile diabetes, Parkinson's, Alzheimer's, and other genetic diseases, could reveal how such diseases develop and provide novel treatment for them. For example, normal cells might be made to replace abnormal ones that cause juvenile diabetes and Alzheimer's disease. It should be possible to coax these newly created embryonic cells "into replacement cells and even organs," says biologist Chad Cowan who participated in the experiments. "But it would definitely not be possible to clone the person from which the adult cell came."
These potentials are not just around the corner. "We feel this is an important achievement," notes Cowan. "We're very excited about it. But we have many technical hurdles to overcome before we're ready for the showroom floor, before we can wheel out the prototype model."
Although the fusion method is more efficient and it satisfies many ethical concerns, he continues, "the achievement does not mean ongoing research using embryonic stem cells should be stopped or even slowed. Our technique may complement that of using these embryonic stem cells - even replace it some day - but that day is a long way off."
Cowan is the lead author of a report of the research published in the Aug. 26 issue of Science. The other authors are Kevin Eggan, Douglas Melton, and Jocelyn Atienza of the Harvard Stem Cell Institute.
Overcoming the hurdles
The next step is to puzzle out how an embryonic cell can turn back, or reprogram, the genes of an adult cell. That could take 10 years, Cowan guesses. "But is will eventually happen, and it will mean scratching at some of biology's fundamental questions in the process," he says.
However, this long-term scratching at the fundamentals does not have to delay the use of hybrid cells for helping patients. The quickest way to new treatments, the researchers believe, is finding a way to remove the embryonic DNA. "That's the primary hurdle in the footrace to find treatments for patients, " Eggan states.
The hybrid cells contain two sets of DNA, or genes, one from the reprogrammed adult cell and one from the embryonic "starter" cell. To track disease development, experimenters need to excise the latter. That done, they can determine how the adult cells differentiate into diseased cells and tissues.
"This seems like the simplest and fastest approach," Cowan comments, "but my experience in biology is that the simplest things sometimes turn out to be the most difficult." This is why none of the researchers will venture a guess on when it could happen, and why they advise against any slowdown in research that requires embryos to be created or destroyed.
The Harvard group obtained the starter cells by growing embryos from excess fertilized cells acquired from fertilization clinics with the owners' permission. Using such materials, Douglas Melton, the Thomas Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences and co-director of the Harvard Stem Cell Institute, has created at least 17 new lines of embryonic stem cells using private funds (see March 4, 2004, Gazette). These are not part of the cell lines eligible for federal funding.
The new work on hybrids was done using stem cells made by Melton, then some of the experiments were repeated with a federally approved line of cells. The adult cells came from foreskin and pelvic areas.
When all the problems are solved, the Harvard team sees a new source of stem cells produced without the need to create or destroy embryos that some people insist are "alive." "We will never satisfy all of the ethical objections to using embryonic stem cells," Cowan admits, "but we believe that the majority of people will find this technique morally acceptable."