Matters of the heart are always complicated (Just ask Dr. Phil!), but this is especially true when appropriate cardiac models aren’t available to medical researchers. Fortunately, a reverse engineering team from Harvard has found a way to combine the CRISPR/Cas9 genome editing system and induced pluripotent stem cells (iPSC), to create a “heart-on-chip” technology that’s able to model the precise mutation causing a heart abnormality and use it to generate some synthetic hearts from patients for groundbreaking observations.
The disease of interest? Barth Syndrome (BTHS), a disorder of the mitochondria caused by a mutation in the TAZ gene. Here’s how heart-on-chip was designed:
- First, induced pluripotent stem cells (iPSCs) were derived from patients with BTHS, which were then coerced into heart cells.
- The new heart cells were then placed on a chip containing a designed extracellular matrix, which developed into a synthetic heart-on-chip.
- Characterizing BTHS at the molecular and organ level, they observed that the hearts contracted weakly due to excess reactive oxygen species (ROS).
- The team went on to show that this single mutation in TAZ was the causative factor of the phenotype.
The heart-on-chip example shows off the great potential of emerging molecular technologies and demonstrates how they can be used to solve the mysteries of modern medicine. Senior author Kevin Parker shares that “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.”
Don’t miss a beat in Nature Medicine, May 2014