Researchers in Japan and Wisconsin report major advance in stem cell research

“The field is moving at lightning speed,” said Harvard Stem Cell Institute (HSCI) Co-Director Doug Melton in response to just-published papers by Japanese researchers and researchers at the University of Wisconsin reporting reprogramming adult human skin cells to produce cells similar to human embryonic stem cells. 

But Melton and other researchers are cautioning that it is much too soon to consider the work by Shinya Yamanaka and colleagues, at Kyoto University, and James Thompson, at the University of Wisconsin, an alternative to research based on the use of human embryonic stem cells, which require the destruction of blastocysts to extract the cells. “This is an exciting advance, and it’s likely to be very valuable,” Melton said, cautioning that “we have to remember that this is still using retroviruses, which are a real limitation. Still, this is one more important step showing that this method is probably going to work eventually. It’s hard for me at this point to see it be applicable to treating human disease. But I’m just delighted.”

Yamanaka’s work, published online today (Nov. 20) by the journal Cell, involves using four factors — including cancer genes — that are inserted into human adult skin cells using retroviruses. It was only last summer that he, Konrad Hochedlinger of HSCI and the Massachusetts General Hospital Center for Regenerative Medicine, and Rudolph Jaenisch, of the Whitehead Institute and MIT, independently and simultaneously reported doing the same thing using mouse skin cells. Because the method involves the use of cancer genes and retroviruses — which can turn on cancer genes — there is general agreement that such cells could not be used to treat patients.

Thompson’s work is published in the journal Science.

 Human embryonic stem cells are able to differentiate into any cell type in the body, and researchers believe that they hold enormous promise as either direct treatments for a host of chronic diseases — including diabetes, cancers, heart disease, and numerous neurodegenerative conditions — or as targets against which chemicals could be screened to develop new pharmaceutical treatments for those same diseases. Melton, who is Co-Director of Harvard's inter-school Department of Stem Cell and Regenerative Biology, and HSCI principal faculty members Kevin Eggan and George Daley have the approval of University and hospital oversight groups to do somatic cell nuclear transfer experiments — producing disease- and patient-specific stem cells by cloning the cells of patients.

Hochedlinger, who last summer published a study similar to Yamanaka’s mouse study, said of Yamanaka’s latest report, “We have to get rid of the viruses. We don’t want retroviruses in the cells. They could activate oncogenes, or be turned on inappropriately in mature cells and cause cancer.” Hochedlinger cautioned that “there are still major hurdles that need to be overcome before thinking about replacing human embryonic stem cells with these cells.”

In fact, Yamanaka supports that assessment. He, Hochedlinger, and Jaenisch, joined by Insoo Hyun, of the Department of Bioethics at Case Western Reserve School of Medicine, coauthored a letter published recently in the journal Cell Stem Cell titled “New Advances in iPS Cell Research Do Not Obviate the Need for Human Embryonic Stem Cells."

“We hold that research into all avenues of human stem cell research must proceed together,” the researchers wrote. “Society deserves to have the full commitment of scientific inquiry at its service. And science is a practice that works best when it is  approached with an open and creative mind. Research into one approach can inspire new ideas in unpredictable and exciting ways.”

Eggan, who himself published a paper on an alternative method of producing cells with the properties of embryonic stem cells, called Yamanaka’s latest finding “a wonderful result,” but went on to warn that “all the problems that existed with animals are still here. The use of retroviruses has been shown to cause cancer in gene therapy, plus there’s a direct use of oncogenes here," in the Yamanaka work.

“This shows that in principle this works in humans,” Eggan said, “but these cells are modified in such a way that you could never use them for human therapy. These things could be used for disease modeling” — creating a disease in a dish in order to study its natural progression — “but that has to be tried.”

Melton predicted that today’s news will be used by opponents of human embryonic stem cell research to argue that it should be stopped until this new method can replace it.“People will be saying this experiment suggests that we shouldn’t be using human embryos,” said Melton, whose laboratory has produced most of the embryonic stem cell lines now being used by researchers around the world.

“Until the alternative is shown to produce the same kind of extremely versatile, normal cells that we derive from previously frozen human blastocysts, it would be unfair to patients to renounce that approach.

“However,” he continued, “we appear to be closer than we ever thought we might be to a day when we could use this alternative method. I’d welcome this other method because it’s easier to obtain the material, and doesn’t raise ethical questions that some find troubling." Equally importantly, he said, is the fact that using this other approach should enormously increase the amount of funding available for the research.