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Two groups of scientists appear to have independently achieved one of regenerative medicine’s holy grails: reprogramming human adult cells to behave like embryonic stem cells, without the use of an embryo or a human egg. The method could provide a way to make patient-specific stem cells, a feat not yet achieved in humans. Such cells could eventually be used for studying complex genetic diseases, or for cell or tissue transplants without fear of immune rejection.

The new technique also removes the major ethical objections to embryonic stem-cell research: the creation and destruction of human embryos. “It’s been 10 years since we derived the first embryonic stem-cell lines, which unleashed a storm of controversy that has lasted until today,” says James Thomson, a biologist at the University of Wisconsin-Madison who isolated the first human embryonic stem cells in 1998 and led the new work. “I believe these results are the beginning of the end of this controversy.”

Two groups–one led by Shinya Yamanaka at Kyoto University, in Japan, and one led by Thompson and Junying Yu at the University of Wisconsin–separately engineered human skin cells to express four different genes. For reasons not yet clear to scientists, exposing cells to these genes appears to turn back the developmental clock. Both groups found that the resulting cells exhibit two major properties that define embryonic stem cells. They are pluripotent, meaning that they can develop into any type of cell in the body, and they can divide apparently indefinitely in their undifferentiated state.

“I’d welcome this other method because it’s easier to obtain the material and doesn’t raise ethical questions that some find troubling,” says Doug Melton, director of the Harvard Stem Cell Institute. “Equally importantly, using this other approach should enormously increase the amount of funding available for the research.”

Embryonic stem cells have been the target of both hype and hope due to their potential ability to replace cells damaged in diseases such as Parkinson’s and diabetes. They are also the source of ethical controversy: the cells are derived from excess human embryos discarded after in vitro fertilization, and obtaining them requires destruction of the embryos. President Bush severely restricted federal funding of embryonic stem-cell research in 2001.

Beyond reprogramming’s potential impact on the ethical debate surrounding embryonic stem cells, one of its biggest advantages is that it provides an alternative way to produce stem cells that are genetically matched to an individual. Reprogrammed, pluripotent cells derived from an individual’s skin cells could eventually be used for tissue transplants without risk of immune rejection. Cells derived from someone with Parkinson’s or diabetes could provide scientists with new models for studying these complex genetic diseases. (See “Stem Cells Reborn” and “The Real Stem Cell Hope.”)

The only other way to produce such cells–human therapeutic cloning–carries its own technical and ethical issues, and has not yet been achieved. It also requires human eggs, which have proved to be extremely difficult to obtain. (See “Human Therapeutic Cloning at a Standstill.”) Ian Wilmut, the scientist who led the effort to clone Dolly the sheep, announced on Friday that he plans to focus his group’s efforts on reprogramming rather than on cloning.

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Credit: Junying Yu/University of Wisconsin-Madison

Tagged: Biomedicine, stem cells

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