Scientists Reprogram Cells To Heal Broken Hearts

Heart attacks, like any wound, often leave behind scar tissue. But a scarred heart isn't just disfigured, it's weaker -- scar tissue can't contract so the organ loses some of its pumping ability.

If only a fairy could wave a magic wand to transform scar tissue into heart muscle cells.

Well, that transformation has happened in mice -- but the fairy was a team of Duke University Medical Center scientists, and the magic wand was a kind of small molecule called microRNA, which can turn many kinds of genes on or off.

Scientists administered microRNA to scar tissue cells both in petri dishes and in the hearts of living mice, which reprogrammed the scar tissue cells into muscle cells that power the heart; no stem cells or surgery required.

The scientists, led by senior author Victor J. Dzau, reported their findings on Tuesday in the journal Circulation Research.

Scientists need to conduct further studies to examine how the transformed tissue performs compared to the rest of the heart, Dzau said in a telephone interview. And it still remains to be seen if the method works on human hearts.

However, this proof of concept is important in that it shows that scar tissue can be reprogrammed in living animals.

Similar reprogramming may be possible for scar tissues found in other organs including brains and kidneys, Dzau said.

The Duke research is similar to findings reported by Gladstone Institutes scientists in Nature last week. But Gladstone researchers used a different method to reprogram the scar tissue, giving mice a cocktail of three genes instead of microRNA.

The effect was essentially the same. Genes that encouraged the development of heart muscle characteristics were switched on, and the scar tissue gradually metamorphosed into myocardial cells of the heart muscle.

One of the advantages of microRNA over other methods is that microRNA is smaller and easier to deliver in several molecules in a single dose, according to Maria Mirotsou, another co-author on the Circulation Research paper.

Whichever mechanism is used, directly reprogramming mature cells to switch from one type of cell to another would have been unthinkable several years ago. A major breakthrough came in 2007 when scientists reprogrammed adult skin cells into induced pluripotent stem cells that can then be manipulated to become a variety of cell types.

At the time, induced pluripotent stem cells seemed like the best hope for a new wave of tailored treatments for a range of diseases, but the advent of direct reprogramming may make stem cells - whether taken from embryos or engineered from adult cells - superfluous.

We can skip that step now, Dzau said.

Paul Knoepfler, a stem cell biologist at the University of California Davis School of Medicine, wrote that the method from the Nature paper isn't foolproof. Gladstone researchers reported that only about 15 percent of the fibroblasts were transformed into functional heart muscle cells, and it isn't clear if that's efficient enough, he wrote.

Another major concern is that the new heart tissue could cause arrhythmias where the heart beats out of rhythm, sometimes with fatal consequences, Knoepfler wrote on his blog.