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Patient stem cells used to make 'heart disease-on-a-chip'
Date:5/11/2014

cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease.

"You don't really understand the meaning of a single cell's genetic mutation until you build a huge chunk of organ and see how it functions or doesn't function," said Parker, who has spent over a decade working on 'organs-on-chips' technology. "In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think that's a big advance."

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract.

"The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROSa normal byproduct of cellular metabolism released by mitochondriawhich had not been recognized as an important part of this disease," said Pu, who cares for patients with the disorder.

"We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function," Pu added. "Now, whether that can be achieved in an animal model or a patient is a different story, but if that could be done, it would suggest a new therapeutic angle."

His team is now trying to translate this finding by doing ROS therapy and gene replacement therapy in animal models of Bart
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Contact: Joseph Caputo
joseph_caputo@harvard.edu
617-496-1491
Harvard University
Source:Eurekalert  

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Patient stem cells used to make 'heart disease-on-a-chip'
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