Harvard's heart disease-on-a-chip mimics real tissue and disease

Just last week, Harvard University's Wyss Institute for Biologically Inspired Engineering revealed its latest organ-on-a-chip: a bone marrow microchip that mimics the real thing in humans that's designed for drug testing.

Now, Harvard scientists have combined their organ-on-a-chip technology, first rolled out in 2010, with stem cells to produce functioning human heart tissue carrying an inherited cardiovascular disease. This so-called heart disease-on-a-chip takes the idea of using microchips for drug testing one step further, with the aim of creating a more personalized therapy regimen for individual patients.

The new chip models the cardiovascular disease Barth syndrome, a cardiac disorder caused by mutation of a gene called Tafazzin, or TAZ. Currently untreatable, Barth syndrome often causes a number of symptoms affecting heart and skeletal muscle function. The disorder is X-linked, so only boys will show symptoms.

Collaborating with researchers from the Harvard Stem Cell Institute, Boston Children's Hospital, Harvard School of Engineering and Applied Sciences and Harvard Medical School, the Wyss team took skin cells from two Barth syndrome patients and manipulated them to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, investigators grew the cells on chips lined with human extracellular matrix proteins that imitate their natural environment. This method essentially tricks the cells into joining together as they would if they were forming a diseased human heart. Like the heart muscle in Barth syndrome patients, the engineered diseased tissue contracted very weakly.

The investigators then used genome editing to determine whether the TAZ mutation causes weak contraction in the engineered tissue. When delivering a TAZ gene product to diseased tissue in the laboratory, the therapy corrected the contractile defect. The work is published in Nature Medicine.

The team is now trying to translate this finding by conducting gene replacement therapy in animal models of Barth syndrome to tests its potential benefit.

- see the abstract in Nature Medicine
- read the press release