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Researchers from the University of Washington School of Medicine successfully restored the function of damaged hearts in macaque monkeys using cardiac muscle cells derived from human embryonic stem cells.
The results suggest that the technique will be effective in human patients with heart failure, the leading cause of death in the world.
The majority of heart failure is caused by death of the heart muscle due to heart attacks. Because the heart muscle does not regenerate, the damaged areas are replaced by scar tissue that does not contract. As a result, the heart weakens.
At some point, the heart can no longer pump enough blood to provide the body with the oxygen it needs to function, which gives rise to what is called heart failure. Symptoms include fatigue, deep weakness and difficulty breathing. Currently, there is no way to restore lost muscle function.
For the study, the researchers caused heart attacks in macaques, which were chosen because their size and physiology are similar to those of humans. Heart attacks have reduced the left ventricular ejection fraction of the heart, a measure of the amount of blood that the heart pumps by heart, by 65 to 40%, which is enough to put the animals in heart failure.
Later, the researchers took the cardiac cells that had grown from human embryonic stem cells and injected them into and around the scar tissue of the heart of the macaques.
Each animal received about 750 million of these cardiomyocytes. For comparison, a cell-free version of the solution that was used to inject the stem cells into the treated animals was injected into a control group.
Four weeks after treatment, the researchers found that the ejection fraction of untreated control animals remained essentially unchanged at about 40 percent; but in treated animals, the ejection fraction had increased to 49.7%, about half of its normal operation.
Magnetic resonance imaging showed that the new heart muscle had become scar tissue. in treated hearts, whereas no new muscle was observed in untreated animals.
The researchers followed two treated animals and a control animal for three months. The fraction of ejection in the control animal decreased, while the treated animals continued to improve. In 90 days, their ejection fractions reached 66%, essentially normal ejection fractions.
When the researchers studied the heart of animals, they discovered that human heart cells had formed new muscle tissue in the damaged region. The new muscle tissue has replaced 10 to 29% of the scar tissue, integrated into the surrounding healthy tissue and developed in mature heart cells.
The authors of the study state that the purpose of the research is to develop a treatment that can be administered to people shortly after suffering a heart attack, to prevent heart failure. In this perspective, the team of researchers is preparing to conduct clinical trials of the approach in the year 2020.
Reference: Function restoration of cardiomyocytes of human embryonic origin in heart infarction nonhuman primates. Nature Biotechnology, 2018. https://doi.org/10.1038/nbt.4162
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