Sufferers of a heart condition that runs in families and can cause sudden cardiac death, especially amongst the young, could look forward to new treatments for the disease thanks to a novel stem cell technique announced this week.
The disease, known as long QT syndrome (LQTS), leads to a delay in the rate at which heart cells electrically reset themselves between each beat. This can cause the heat beat to become irregular, especially when the heart is under heavy load, and places carriers of the condition at risk of potentially fatal cardiac arrest. But studying the condition, which is caused by abnormalities in a number of different genes, is difficult because it is hard to recreate a model heart cell to study in order to understand the underlying abnormalities. Similarly, without a model cell, it's also much more challenging to develop drugs to alleviate the problem, or identify drugs that actually exacerbate or trigger the disease.
But now Ilanit Itzhaki, who's based at Israel's Institute of Technology in Haifa, has successfully used stem cell technology to culture long QT syndrome cells in a dish so that they can be studied. The work, which is published in Nature, involved first collecting a small number of skin cells called fibroblasts from a patient with one form of LQTS.
Next, a virus was used to add to the cells three genes, called SOX2, KLF4 and OCT4, which caused them to "un-specialise" and become so-called IPSCs - induced pluripotent stem cells, resembling the cells found in an early human embryo. When these cells were grown in a culture dish they then began to transform themselves into many of the different cell types found as an embryo develops, including cells that naturally began to beat like embryonic heart cells.
Studying these cells further revealed that they looked and behaved, both chemically and electrically, like early heart cells. Critically, they also showed electrical abnormalities identical to those seen in adults with LQTS.
Isolating these cells, it was then possible to test them against a range of drugs known to aggravate or ameliorate LQTS to see how these agents were impacting on the electrical behaviour of the cells.
This means that, for the first time, it is possible to produce model cells directly from an affected patient in order to test possible therapies and also to rationally develop novel drugs in vitro. The same approach could also be used to learn more about a range of different diseases, not just heart conditions.
As Itzhaki points out, "The concepts described may also be extended to model several other human genetic disorders, enabling translational research into disease mechanisms and therapies."