Stem cell heart repair treatments could be tested on human patients within four years following a groundbreaking study of monkeys.
Scientists successfully restored damaged cardiac muscle in macaque monkeys suffering the after-effects of experimentally induced heart attacks, paving the way to clinical trials.
Researchers injected one billion immature heart muscle cells derived from human embryonic stem cells (hESCs) into each animal's heart.
Over a period of several weeks, the new cells developed, assembled into muscle fibres, and began to beat in correct time.
On average, 40% of the damaged heart tissue was regenerated.
It is the first time stem cell therapy for damage caused by heart attacks has been shown to work in a primate.
Lead scientist Charles Murry, director of the Centre for Cardiovascular Biology at the University of Washington in Seattle, US, said: “Before this study, it was not known if it is possible to produce sufficient numbers of these cells and successfully use them to re-muscularise damaged hearts in a large animal whose heart size and physiology is similar to that of the human heart.”
He added that he expected the treatment to be ready for clinical trials in human patients within four years.
Heart attack symptoms were triggered in the monkeys by blocking the coronary artery - the main artery supplying the heart with blood - for 90 minutes.
In humans, the reduced blood flow caused by narrowing of the arteries has a similar effect.
Lack of blood flow to the heart damages the heart muscle by depriving it of oxygen.
The lost tissue cannot grow back, so that even if a patient survives an attack the heart is seriously weakened.
Often this leads to heart failure, a debilitating and potentially fatal condition caused by insufficient blood being pumped around the body.
The scientists waited two weeks before testing the stem cell treatments on the heart-damaged macaques.
Immature heart cells called cardiomyocytes were grown from embryonic stem cells in the laboratory and injected into in the animal's hearts.
The numbers of cardiomyocytes used was large – 10 times more than researchers had ever been able to generate before.
After three months, the cells appeared to have fully integrated into the heart muscle, the team reported in the journal Nature.
“The results show we can now produce the number of cells needed for human therapy and get formation of new heart muscle on a scale that is relevant to improving the function of the human heart,” co-author Michael Laflamme, also from the University of Washington, said.
Ultrasound studies showed that ejection fraction – a measurement of the heart's ability to pump blood – had improved in some but not all of the treated animals.
Arteries and veins from the monkeys’ hearts were also found to be growing into the new heart tissue, the first time this had been seen.
Although the macaques experienced episodes of irregular heart beat after the injections, these disappeared after two or three weeks as the cells matured and became more electrically stable.
Further work will focus on reducing the risk of irregular heartbeats, or arrhythmias, possibly by using more mature cardiomyocytes.
Attempts will also be made to demonstrate definitively that the injected cells strengthen the heart's pumping power.
“These cells have improved the mechanical function in every other species in which they have been tested, so we are optimistic they will do so in this model as well,” Murry said.
Peter Weissberg, medical director of the British Heart Foundation, said: “This research brings us one step closer to repairing a damaged human heart, but we still have some way to go until we reach our goal.
“Researchers showed that heart cells derived from human stem cells in a laboratory can survive and function alongside normal heart cells inside a damaged monkey heart. However, the monkeys had to be given anti-rejection drugs and some hearts showed no improvement in function - the main aim of this field of research. The cells also caused worrying heart rhythm disturbances.
“So there are still many hurdles to overcome before we have an effective and reliable cell-based treatment for heart failure patients, but these results demonstrate encouraging progress. The goal of our Mending Broken Hearts Appeal is to fund innovative research to overcome these hurdles and make these types of treatments a reality.”