Stem cells can be used to heal scars after heart attacks, bringing regenerative treatments a step closer.
The study found the amount of permanent scarring on the heart was reduced by half compared to conventional treatment and led to the development of new muscle.
However, the treatment produced no significant change in "ejection fraction" - a measure of the heart's pumping capacity.
The Caduceus trial recruited a total of 25 patients with an average age of 53 who had all suffered a heart attack in the previous month.
Seventeen received coronary artery infusions of 12 to 25 million stem cells derived from healthy tissue taken from their own hearts.
The remaining eight underwent standard post-heart attack care.
A year later, the proportion of the heart left scarred in the stem cell-treated patients had been reduced from 24% to 12%. No change was seen in patients who did not receive the treatment.
Professor Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, who led the US team, said: "The effects are substantial, and surprisingly larger in humans than they were in animal tests.
"This discovery challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored."
Future work will need to see if stem cell treatment can bring any long-term improvement in patients who experience heart failure after a heart attack.
This occurs when a weakened heart is not strong enough to pump sufficient blood around the body, causing breathlessness and exhaustion.
Professor Jeremy Pearson, associate medical director at the British Heart Foundation (BHF), said: "It's early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure."
The BHF's Mending Broken Hearts appeal aims to raise £50 million for research into regenerative heart treatments.