|Heart muscle cells generated from patient skin samples|
The condition comes on when a person is in their 20s. Using stem cells created from a patient’s skin, the scientists created heart tissue. But those youthful cells showed no sign of the disease. The scientists had to in essence make the cells old – like in the heart of a 20 year old – before they started showing signs of the disease in a lab dish.
Prior to discovering how to make the cells age, the scientists were in a quandary. They had stem cells that carried the same genetics as the person with the disease, and yet those cells showed no sign of the disease. They were useless for studying the disease or looking for new drugs.
In their blog, Sanford-Burnham describes the technique like this:
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.Once the team was able to mimic the disease in a lab dish, they found a molecule that might be at the heart of the disease (as it were). Chen recently received a CIRM Basic Biology IV award to find therapies for the disease using this model.
The work was published in the January 27 issue of Nature.
CIRM funding: Huei-sheng Chen (RS1-00171-1, RB2-01512 and RB4-06276)