Kevin Kit Parker (Harvard University)
12 May 2014. Medical and engineering researchers from Harvard University and affiliated hospitals created heart tissue with a genetic disorder on a chip-like device in the lab using stem cells. The results point to a new method for personalized lab testing of therapies for cardiac patients with cells derived from their own tissue, as well as potential therapies for Barth syndrome, a serious heart condition.
The team led by biomedical engineering professor Kevin Kit Parker and cardiologist William Pu published their findings yesterday online in the journal Nature Medicine (paid subscription required). The authors include researchers at University of Southern California, Kennedy Krieger Institute in Baltimore, University of Washington in Seattle, and Academic Medical Center in Amsterdam, the Netherlands.
Parker, Pu, and colleagues created functioning heart cells with Barth syndrome, an inherited disorder caused by a mutation in the tafazzin gene that produces cardiolipin, an oil in the body essential for producing energy for the heart and skeletal muscles. Barth syndrome affects mainly boys, has no cure, and can lead to cardiac failure and severe infections.
The researchers took skin cells from two patients with Barth syndrome, and cultured the cells to derive stem cells with the tafazzin gene mutations. The stem cells were then grown on microfluidic lab chips like those used to recreate organ functions, a field in which Harvard’s Wyss Institute has experience. The chips already had human structural cell proteins — the kind that support cell growth — which encouraged the stem cells to develop into heart muscle cells, and in this case the tissue also exhibited the weak heart rhythms found in patients with Barth syndrome.
Creating heart tissue in the lab made it possible for the team to learn more about way the mutation causing Barth syndrome operates and the development of the disease. They discovered the mutation disrupts the cells’ energy functions, but through a separate path from the usual energy-producing process. The researchers found the mutation appears to cause a release of excessive reactive oxygen species, a normal byproduct of cell metabolism, but in excess can cause damage in the body, including to oils like cardiolipin.
The team also used the lab-grown heart tissue to test a potential gene therapy for Barth syndrome. They enlisted the help of Harvard geneticist George Church, who developed genomic editing techniques that made it possible to mutate the tafazzin gene in normal cells, causing the same kind of weak heartbeat found in the cells from Barth syndrome patients. In addition, they report the delivery of healthy tafazzin genes to the diseased tissue in the lab, corrected defects in the heart tissue’s contractions.
Parker, Pu, and colleagues next want to develop their process of recreating heart tissue on a lab chip into a testing platform for drugs. In addition, the researchers are pursuing the findings on gene replacement and reactive oxygen species as avenues for therapies to treat Barth syndrome.
Read more:
- Lab-On-Chip Diagnostics Company Lands $2.1M Angel Financing
- FDA Funds Organ-on-Chip to Test Radiation Disease Treatments
- Lab-On-A-Chip Diagnoses Multiple Tropical Diseases
- Lab-On-Chip Maker Lands $9.2M in Early Round Venture Funds
- Harvard Institute, Sony to Partner on Organs-on-Chips
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