Harvard researchers have grown a section of the human heart for testing, complete with an inherited cardiovascular disease.

The scientists have merged stem cell and ‘organ-on-a-chip’ technologies to grow the functioning human heart tissue, working proof that a chunk of tissue containing a specific genetic disorder can be replicated in the laboratory.

A cross-discipline team has published its latest study in the journal Nature Medicine, after bringing together experts in medicine, stem cell production and engineering.

Using their combined approach, the investigators modelled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ.

Researchers took skin cells from two Barth syndrome patients and manipulated the cells to become stem cells with the TAZ mutations intact.

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 edited the genome to mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue.

The contraction is displayed in the following video; 

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 organ-on-a-chip specialist Kevin Parker.

“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.”

The team also discovered that the TAZ mutation works to disrupt the normal activity of mitochondria, the power plants of the cell, but the mutation did not appear to impact the overall energy supply of the cells.

In what may be a newly-identified function for mitochondria, the researchers further described a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract.

“We showed that, at least in the laboratory, if you quench the excessive ROS [reactive oxygen species] production then you can restore contractile function,” one researcher commented.

“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.”