Scientists Build Barth Syndrome Heart Disease-On-A-Chip
Scientists from Harvard have combined stem cell research and ‘organ-on-a-chip’ technologies to build the first ever functioning human heart tissue with Barth Syndrome, an inherited cardiovascular disease.
The milestone achievement helps widen prospects for personalized medicine in the future, as growing a patient’s specific genetic disorder in a lab replication is now possible.
Barth Syndrome is a rare X-linked cardiac disorder that results from the mutation of the single gene Tafazzin (TAZ). The disease mostly affects boys and is linked with several heart and skeletal muscle symptoms. Barth Syndrome currently has no therapy or cure.
Using skin cells taken from two Barth Syndrome patients, the researchers manipulated the cells to convert into stem cells carrying TAZ mutations. The stem cells were grown on chips lined with human extracellular matrix proteins to simulate their natural environment. The stem cells responded by joining together as if forming a diseased heart with Barth syndrome. Scientists reported that the engineered diseased heart tissue contracted weakly similar to a natural diseased heart muscle.
Organs-on-chips expert Kevin Kit Parker said, “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. 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 used genome editing to deliver TAZ gene product to the lab-grown diseased tissue and found that it corrected the weak contractile effect, making it the first tissue-based model of a genetic heart disease correction.
Stem cell expert and a cardiologist at Boston Children’s Hospital William Pu described how the TAZ mutation-induced Barth syndrome cells generated an excess amount of reactive oxygen species (ROS), which has not been previously recognized as a disease factor. “We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function. 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,” said Dr. Pu.
The research team is now trying to leverage the findings by experimenting with ROS therapy and gene-replacement therapy in animal models of the disease. The scientists are also using their ‘heart disease-on-a-chip’ technology to test the abilities of approved and candidate drugs to treat the heart disorder.
The researchers’ work is the result of collaboration between the Wyss Institute for Biologically Inspired Engineering, Boston Children’s Hospital, Harvard Stem Cell Institute, and other Harvard affiliations. Results of the study were published in the journal Nature Medicine.