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When researchers announced two years ago that they had found a way to turn ordinary skin cells into stem cells, it opened up the possibility that stem cell therapies might sidestep the logistical and ethical hurdles of obtaining stem cells from embryos. These “reprogrammed” stem cells seem to have the ability to transform into any kind of cell, a property known as pluripotency. But the concept has also met with skepticism about the abilities and potential dangers of the cells. A new study in the Proceedings of the National Academy of Sciences by scientists at MIT and Harvard shows that reprogrammed cells, also called induced pluripotent stem (iPS) cells, can become functioning neurons when transplanted into the brains of mice and rats; the researchers also showed that the cells can improve symptoms in a rat model of Parkinson’s disease.

The research team, led by Rudolph Jaenisch at the Whitehead Institute for Biomedical Research at MIT, used the previously developed method for reprogramming cells, in which skin cells of a mouse can be made pluripotent when infected with a retrovirus carrying four genes. First, the scientists showed that they could turn mouse skin cells into functioning neurons in culture. They then transplanted these neurons into the brains of mice while they were still fetuses. After the mice grew into early adulthood, the researchers examined the brains and identified the transplanted cells, which had been labeled with a fluorescent marker. The cells “migrate nicely into the brain and mature in the brain,” says Marius Wernig, a postdoctoral fellow at the Whitehead Institute. “They adopt functions of mature neurons.”

Next, the group tested whether these functioning neurons could repair a defect in an animal model of disease. Parkinson’s involves a loss of a specific population of neurons—-those that produce dopamine. The study used a model for Parkinson’s in which rats are given a toxin that kills dopamine neurons on one side of the brain. Although the animals appear normal, when their dopamine neurons are stimulated with amphetamine, they begin to turn in circles in the direction of the damaged side. In rats that were given transplants of neurons derived from iPS cells, the motor defect improved.

John Gearhart, a stem cell biologist at Johns Hopkins School of Medicine who was not involved in the study, says that previous studies with the reprogrammed cells have had conflicting results–some studies show that the cells have similar abilities as embryonic stem cells, while others don’t. “This is an important study,” says Gearhart, because it compares the iPS cells with neurons derived from embryonic stem cells.

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Credit: National Academy of Sciences, PNAS.

Tagged: Biomedicine, MIT, stem cells, Parkinson's, reprogramming cells, skin cells

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