Image Caption: Researchers use modified RNA transfection to correct genetic dysfunction in heart stem cells derived from Barth syndrome patients. The series of images show how inserting modified RNA into diseased cells causes the cells to produce functioning versions of the TAZ protein (first image: in green) that correctly localize in the mitochondria (second image: in red). When the images are merged to demonstrate this localization, green overlaps with red, giving the third image a yellow color. Credit: Gang Wang and William Pu/Boston Children's Hospital

[ Watch The Video: Cardiac Tissue Contractile Strength Differences Shown Using Heart-On-A-Chip ]

Harvard University

Harvard scientists 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 patients specific genetic disorder can be replicated in the laboratory.

The work, published in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Childrens Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

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.

You dont really understand the meaning of a single cells genetic mutation until you build a huge chunk of organ and see how it functions or doesnt 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 thats 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 didnt 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 cells ability to build itself in a way that allows it to contract.

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'Heart Disease-On-A-Chip' Made From Patient Stem Cells