Researchers at the University of Washington Health Sciences (UW Medicine) in Seattle have successfully restored heart function in monkeys with heart failure using human stem cells. The findings, published on July 2, 2018 in Nature Biotechnology, demonstrate the promise of the method in the treatment of patients with heart failure, one of the leading causes of death worldwide.
“The cells form new muscle that integrates into heart so that it pumps vigorously again”, – said Dr. Charles “Chuck” Murry, professor of pathology at the University of Washington School of Medicine, the director of the Institute of Stem Cells and Regenerative Medicine at UW Medicine and senior manager of the research project.
“In some animals the cells returned the hearts’ functioning to better than 90 percent of normal. Our findings show that human embryonic stem cell-derived cardiomyocytes can re-muscularize infarcts in macaque monkey hearts and, in doing so, reduce scar size and restore a significant amount of heart function. This should give hope to people with heart disease.”
The frequent cause of heart failure is heart muscle (myocardium) death as a result of myocardial attacks. Since the myocardium is not restored, the damaged areas are replaced by scar tissue, which is unable to contract. As a result, the pumping function of the heart decreases. At a certain point, the weakened heart can no longer pump enough blood, needed to fully supply the body with oxygen. This is called heart failure.
Symptoms of the disease include edemas, shortness of breath, general weakness and rapid fatigue. The death rate from heart failure is almost 10 times higher than the death rate from myocardial infarction, and the average life expectancy from the beginning of the diagnosis is 5 years, which is even worse than with some oncological diseases. Currently, there is no way to restore the lost function of the heart muscle.
In a new study, American scientists caused an experimental heart attacks in macaque monkeys. Macaques were chosen because their heart size and physiology are close to that of humans. The infarction reduced the hearts’ left ventricular ejection fractions (a measure of how much blood the heart pumps per beat) from about 65 to 40% – enough to cause heart failure in the animals.
Two weeks later the researchers took heart cells that they had grown from embryonic human embryonic stem cells (ESCs) and injected them into and around the young scar tissue. Each animal received an injection of a solution containing approximately 750 million ESC-derived cardiac cells. A similar solution containing no cells was added to the control group for comparison.
The researchers found that, at four weeks after the start of treatment, the fraction of the control group’s release remained almost unchanged, it stayed at about 40%. And in macaques that received stem cells, the ejection fraction had risen to 49.7 percent, about half-way back to normal.
Magnetic resonance imaging, or (MRI) scans showed that new heart muscle had grown within what had been scar tissue in the treated hearts, while no new muscle was seen in the untreated animals.
The researchers followed two treated animals and one control animal for three months. During this period, the volume of the ejection fraction in the control animal declined, while in the second group, Their ejections fractions rose from 51%, at four weeks after treatment, to 61 and 66% (in fact, close to normal) at three months later.
A study of the structure of the hearts showed that human cardiomyocyte formed a new muscle tissue in the damaged region, which replaced from 10 to 29% of the scar tissue, was integrated into the surrounding healthy tissue and developed into mature heart cells.
Murry said that the purpose of his group’s research is to develop а treatment for people who have recently had a heart attack to prevent the development of heart failure. Because cardiomyocytes are long-lived cells, there should be no need for additional therapy, he said. Genetic modification of transplanted stem cells is also necessary to reduce the risk of immune rejection, which often complicates organ transplantation.
“What we hope to do is create a ‘one-and-done’ treatment with frozen ‘off-the-shelf’ cells that, like O-negative blood, can go into any recipient with only moderate immune suppression”, – Murry said.