Molecular "cocktail" transforms skin cells into beating heart cells

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The power of regenerative medicine appears to have turned science fiction into scientific reality — by allowing scientists to transform skin cells into cells that closely resemble beating heart cells. However, the methods required are complex, and the transformation is often incomplete. But now, scientists at the Gladstone Institutes have devised a new method that allows for the more efficient — and, importantly, more complete — reprogramming of skin cells into cells that are virtually indistinguishable from heart muscle cells. These findings, based on animal models and described in the latest issue of Cell Reports, offer new-found optimism in the hunt for a way to regenerate muscle lost in a heart attack.Heart disease is the world’s leading cause of death, but recent advances in science and medicine have improved the chances of surviving a heart attack. In the United States alone, nearly 1 million people have survived an attack, but are living with heart failure — a chronic condition in which the heart, having lost muscle during the attack, does not beat at full capacity. So, scientists have begun to look toward cellular reprogramming as a way to regenerate this damaged heart muscle.The reprogramming of skin cells into heart cells, an approach pioneered by Gladstone Investigator, Deepak Srivastava, MD, has required the insertion of several genetic factors to spur the reprogramming process. However, scientists have recognized potential problems with scaling this gene-based method into successful therapies. So some experts, including Gladstone Senior Investigator Sheng Ding, PhD, have taken a somewhat different approach.”Scientists have previously shown that the insertion of between four and seven genetic factors can result in a skin cell being directly reprogrammed into a beating heart cell,” explained Dr. Ding, the paper’s senior author and a professor of pharmaceutical chemistry at UCSF, with which Gladstone is affiliated. “But in my lab, we set out to see if we could perform a similar transformation by eliminating — or at least reducing — the reliance on this type of genetic manipulation.”To that effect, the research team used skin cells extracted from adult mice to screen for chemical compounds, so-called ‘small molecules,’ that could replace the genetic factors. …


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