Animal hearts regained close to normal function within four to eight weeks after treatment with the protein patch.
It might be possible to test the patch in human clinical trials as early as 2017, researchers said.
Researchers identified the protein called Follistatin-like 1 (FSTL1), which can stimulate cultured heart muscle cells to divide.
They embedded the protein in a patch and applied it to the surface of mouse and pig hearts that had undergone an experimental form of myocardial infarction or heart attack.
Remarkably, FSTL1 caused heart muscle cells already present within the heart to multiply and re-build the damaged heart and reduce scarring.
Heart muscle regeneration and scarring are two major issues that current treatments for heart attacks do not address, said Professor Pilar Ruiz-Lozano from Stanford University.
"Treatments don`t deal with this fundamental problem - and consequently many patients progressively lose heart function, leading to long-term disability and eventually death," Ruiz-Lozano said.
Most patients survive a heart attack immediately after it happens. But the organ is damaged and scarred, making it harder to pump blood. Sustained pressure causes scarring to spread and ultimately leads to heart failure.
The team initially looked to other species for inspiration. Lower vertebrates, such as fish, can regenerate heart muscle, and prior studies in fish suggested that the epicardium, the heart`s outside layer, might produce regenerative compounds.
The team started with the epicardial cells themselves, and showed that they stimulated existing heart muscle cells, or cardiomyocytes, to replicate.
Researchers used mass spectrometry and high throughput assays to find whether a single compound might be responsible.
They found that FSTL1 did the job. The researchers then developed a therapeutic patch made out of collagen, which was cast with FSTL1 at its core.
Testing the patch loaded with FSTL1 in a heart attack model in mice and pigs showed that it stimulated tissue regeneration even if implanted after the injury.
In pigs that had suffered a heart attack, the fraction of blood pumped out of the left ventricle dropped from the normal 50 per cent to 30 per cent.
But function was restored to 40 per cent after the patch was surgically placed onto the heart a week after injury and remained stable.
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