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Diseased stem cells: Scientists generated a type of nerve cell called an astrocyte (shown here in red) from stem cells created from a patient with amyotrophic lateral sclerosis (ALS). Previous studies suggest that these cells play an important role in the progression of the motor neuron degeneration. The green cells are neurons, while the blue circles highlight cell nuclei.

“It is likely that this will be one of the most important uses of stem cells during the next 10 to 20 years,” said Ian Wilmut, director of the Scottish Centre for Regenerative Medicine, in Edinburgh, in an e-mail. Wilmut, best known for the cloning research that produced Dolly the sheep, was not involved in the current project but is pursuing a similar path.

Because the cells were created using genetic engineering, they are not suitable for therapeutic use. Scientists are now working on ways to reprogram cells using drugs rather than genes. However, therapies using IPS cells to replace the cells damaged in disease are likely years, if not decades, away.

The researchers haven’t yet studied the new motor neurons for signs of disease, but similar experiments in mice hint at the cells’ promise: mouse cells with a mutation in the same gene as that in the ALS patient seemed to reflect the disease. When differentiated into neurons and compared with neurons made from normal stem cells, those that carried the mutation didn’t survive as well as those that did not carry it, says Eggan, who is now using the cells to screen potential new drugs for ALS. “These approaches would be much more powerful if we could do them with actual patient cells,” he says.

The cells should also allow scientists to test specific theories of ALS. For example, in the mouse experiments, the researchers found that another type of neural cell, known as an astrocyte, seemed to produce a toxin that harmed motor neurons. “We’re curious to see if we can make astrocytes from stem cells and if they also have this toxic effect,” says Eggan.

The cell donor in this research has a rare, familial form of ALS linked to a specific genetic variation. Scientists are now trying to derive stem cells from a patient with the more-common sporadic form of ALS, as well as from a healthy control donor, in order to compare healthy and diseased cells.

Eggan first set out to create patient-specific stem cells more than two years ago using therapeutic cloning. In that technique, DNA from an adult cell is inserted into an egg whose DNA has been removed. The egg begins to develop as a normal embryo would, and scientists harvest stem cells after a few days. However, human eggs proved extremely hard to find: Eggan’s group, which is still pursuing cloning, has received eggs from only one donor to date. No one has yet produced stem cells from human therapeutic cloning.

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Credits: Kit Rodolfa and John Dimos at Harvard University

Tagged: Biomedicine, stem cells, diseases, reprogramming, ALS, degenerative diseases

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