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Patients' own skin cells are transformed into heart cells to create 'disease in a dish'
Date:1/27/2013

one of the largest ARVD/C patient registries in the world.

"There is currently no treatment to prevent progression of ARVD/C, a rare disorder that preferentially affects athletes. With this new model, we hope we are now on a path to develop better therapies for this life-threatening disease," said Judge, associate professor and medical director of the Center for Inherited Heart Disease at the Johns Hopkins University School of Medicine.

Disease in a dish

To recreate a person's own unique ARVD/C in the lab, the team first obtained skin samples from ARVD/C patients with certain mutations believed to be involved in the disease. Next they performed Yamanaka's technique: adding a few molecules that dial back the developmental clock on these adult skin cells, producing embryonic-like induced pluripotent stem cells (iPSCs). The researchers then coaxed the iPSCs into producing an unlimited supply of patient-specific heart muscle cells. These heart cells were largely embryonic in nature, but carried along the original patient's genetic mutations.

However, for nearly a year, no matter what they tried, the team couldn't get their ARVD/C heart muscle cells to show any signs of the disease. Without actual signs of adult-onset ARVD/C, these young, patient-specific heart muscle cells were no use for studying the disease or testing new therapeutic drugs.

Speeding up time

Eventually, the team experienced the big "aha!" moment they'd been looking for. They discovered that metabolic maturity is the key to inducing signs of ARVD/C, an adult disease, in their embryonic-like cells. Human fetal heart muscle cells use glucose (sugar) as their primary source of energy. In contrast, adult heart muscle cells prefer using fat for energy production. So Chen's team applied several cocktails to trigger this shift to adult metabolism in their model.

After more trial and error, they discovered that metabolic malfuncti
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Contact: Heather Buschman
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

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