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Patient-derived induced stem cells retain disease traits
Date:12/21/2008

at the scene of a road accident the car's in the ditch, but they don't know how it got there or the cause of it," explains Svendsen, a professor of anatomy and neurology in the UW-Madison School of Medicine and Public Health and the Waisman Center, and co-director of the Stem Cell and Regenerative Medicine Center.

With iPS cells, he says, "Now you can replay the human disease over and over in the dish and ask what are the very early steps that began the process. It's an incredibly powerful new tool."

In the new study, the researchers created iPS cells from stored skin cells of a young SMA patient and his mother, who does not have the disease. The cells grew well in the lab, and the group developed a new method to efficiently drive them to make large numbers of motor neurons, the cells that control muscles and that are affected in SMA.

Initially, the motor neurons thrived in both samples. But after about a month, "the accident started happening," Svendsen says, and the motor neurons from the patient-derived cells began to disappear.

"The motor neurons we got started to die in culture, just like they do in the disease. This is the first validation of a human disease that we've modeled in a culture dish," he says.

They can now begin to dissect what kills the motor neurons and why these cells alone are targeted in the disease. Past studies to understand the effects of the SMA-causing mutation have often relied on the easy-to-obtain skin cells, which are not affected in SMA and offer limited insight into how and why motor neurons die, says UW-Madison researcher Allison Ebert, lead author on the new study.

"If we start to understand more of the mechanism of why the motor neurons specifically affected in the disease are dying, then potentially new therapies can be developed to intervene at particular times early in development," she explains. Current SMA treatment options are limited, and there is no cure.<
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Contact: Clive Svendsen
cnsvendsen@wisc.edu
608-265-8668
University of Wisconsin-Madison
Source:Eurekalert

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