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Washington, May 12 : Researchers have merged stem cell and 'organ-on-a-chip' technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease.

The research appears to be a big step forward for personalized medicine, as it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

Using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart.

The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients.

The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to 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.

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.

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Stem cell and 'organ-on-a-chip' merger step forward for personalized meds

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