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Researchers at the University of Washington, Seattle, used cardiomyocytes derived from human embryonic stem cells (hESC-hc) to restore heart function in macaques with heart failure. The researchers hope that their realization could pave the way for the development of a similar treatment for human patients.
Studies on macaques have shown that transplanted hESC-CMs have developed into ventricular myocytes and formed electromechanical junctions with the animals' own heart tissue. in significant improvements in left ventricular function, and thus the ability of the heart to pump blood. "In some animals, the cells made the heart function more than 90% normal," says Charles Murry, MD, a professor of pathology at the University of Washington School of Medicine, who said directed the research team. the United States, Ireland, Russia and Taiwan. "This should give hope to people with heart disease." Dr. Murry is also a Professor of Medicine in the Division of Cardiology and Bioengineering, and Director of the UW Medicine Institute for Research on Diseases. stem cells and regenerative medicine
. Researchers report their work in Nature Biotechnology in an article titled "Restoring function of cardiomyocytes derived from human embryonic stem cells in hearts infested with non-human primates."
Heart disease is the leading cause of death worldwide, at least in part because the heart has a very limited regenerative capacity.After a heart attack, damaged areas of the heart muscle are replaced by tissue scar, which has no contractile capacity. When the heart is no longer able to pump enough blood to supply the body with oxygen, the result is heart failure, which affects about 6.5 million people in the United States and causes more than 600,000 deaths. Current drug treatments can manage the symptoms, "but do not address the basic problem of muscle deficiency," the authors point out
. Over the last 20 years, we have increasingly focused on the development of cell therapies. promote cardiac regeneration, including the use of human cardiomyocytes derived from hESCs. Previous studies have shown that cardiomyocytes derived from hESCs can survive and form new myocardial tissue that improves cardiac function in animal models of myocardial infarction.
For their latest studies, the authors evaluated intracardiac grafts of hESC-CM in the macaque, a primate. This represents a physiologically relevant large animal model. "This model should provide the best possible prediction of the human response to hESC-CM transplantation," the team suggests. "The central hypothesis of this study was that hESC-CM would reminulate the hearts of macaques and restore their function after myocardial infarction."
The researchers induced experimental heart attacks in monkeys, which after two weeks had reduced the left ventricular ejection fraction (LVEF) – a measure of the pumping capacity of the heart – to about 40% of the normal. It was enough to put the animals in heart failure.
Two weeks after infarction, the animals then received hESC-CM injections directly into the damaged areas of the heart and surrounding heart tissue. Cardiac function was then monitored using techniques including magnetic resonance imaging (MRI). The results showed that if LVEF in animals receiving simulated injections decreased steadily over the next three months, LVEF in animals receiving hESC-CMs improved on average by 10.6% after one month. and three months of 12.4%. The ejection fractions of two treated animals followed for three months continued to increase by 51% at four weeks after treatment, to 61% and 66% – essentially normal ejection fractions – at the point of three months. month. "The 20% absolute improvement in the LVEF observed in both hESC-CM hearts studied at 3 months was striking and shows that substantial mechanical improvement can occur between 1 and 3 months," say the authors.
Grafts in treated animals About 11% of the size of the infarct were shown to form electromechanical junctions with the heart of the host. At 3 months, the grafted tissue contained about 99% ventricular myocytes, the authors state.MRIs further confirmed that the new heart muscle had increased scar tissue in treated hearts
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