The Stanford team collected skin cells from four people in a family that has an inherited form of dilated cardiomyopathy: a grandmother, two of her sons and a grandson. The fourteen year old grandson has such a severe form of the disease that he had already required a transplant. They then converted those cells to an embryonic-like state, called an iPS cell, and coaxed the cells to mature into heart tissue.
A Stanford press release describes their findings:
Wu and Sun also saw that the diseased cells exhibit structural differences and are more susceptible to mechanical stress than unaffected cells.In addition to providing a way of understanding and finding therapies for this disease, the researchers say their approach could help test drugs for toxicity.
When the researchers treated the diseased cells with metoprolol, a beta blocker commonly used to treat cardiomyopathy, they found that it decreased the frequency of contractions as expected. It also increased the responsiveness of the cells to calcium and, over time, helped resolve some of the structural differences between affected and unaffected cells. What’s more, the team tried a gene therapy approach that is currently in clinical trials and found that it also improved the forcefulness of the cells’ contractions.
According to the Stanford release:
The implications of such research are huge. According to Wu, one of the major reasons cardiac drugs are pulled from the market is unexpected cardiac toxicity — that is, they are damaging the very hearts they’re meant to help. Currently, such drugs are pre-screened for toxic effects on common laboratory cell lines derived from either hamster ovaries or human embryonic kidney cells. Even though these ovarian and kidney cells have been artificially induced to mimic the electrophysiology of human heart cells, they are still very different from the real thing. A reliable source of diseased and normal human heart cells on which to test the drugs’ effect prior to clinical use could improve drug screening, save billions of dollars and improve the lives of countless patients.This issue of testing drugs for possible side effects is one other CIRM grantees are also working on. We produced a video a few years ago with Bruce Conklin of the Gladstone Institutes talking about this approach.
CIRM Funding: Joseph Wu (RB3-05129)