The damaged hearts of laboratory monkeys have been successfully repaired for the first time with human stem cells in a study that could lead to the first clinical trials on patients with heart disease within the next four years, scientists said.
The study, published in the journal Nature, demonstrates that human stem cells can be grown in large enough quantities to form beating cardiac muscle tissue which can be stored in frozen form until needed for a transplant operation, the researchers said.
Experiments involving the injection of human stem cells into the damaged hearts of mice, rats and guinea pigs have already shown the potential for treating heart disease but the latest study is the first to prove its potential in a non-human primate species, the pintail macaque monkey.
“The main significance of this study is that it shows for the first time that we can do heart regeneration at a scale that the world has never seen before,” said Charles Murry, professor of pathology and bioengineering at the University of Washington in Seattle.
“We’re able to grow large amounts of human heart muscle cells in a dish. We can grow them in the billions, we can freeze them and keep them in cold storage until we can use them and then we can transplant them into the heart of a large animal that really mimics the human condition well,” Professor Murry said.
Stem cells, sometimes known as the “master cells” of the body, are seen as offering new kinds of treatments for incurable or progressive illnesses, from heart disease to Parkinson’s, but there are still immense practical and safety issues before they can be widely introduced.
For treating human heart disease, for instance, it will be necessary to grow billions of cardiac muscle cells in the laboratory from stem cells and to freeze them without impairing their ability to regenerate damaged cardiac muscle once they have been implanted into a patient, Professor Murry said.
“The principal focus is to understand stem cells to the point where we can grow large amounts of beating human heart muscle in a dish, to learn the science of how they differentiate and then to harness them in such a way that we can cure human heart disease ultimately,” he 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 explained.
The study was carried out on just seven macaque monkeys suffering from a condition that simulated human heart disease. In each case, the animal showed an improvement with the implanted human stem cells leading to an average 40 per cent repair of the damaged tissue.
After three months, the implanted cells appeared to have fully integrated with the monkey’s own cardiac tissue, beating in synchrony and with the primate’s blood vessels growing into and nurturing the replacement cells.
“Once in the heart we’ve shown they survive, that they are able to organise themselves into new heart muscle and they will connect with the surrounding cardiac muscle cells and beat in synchrony,” Professor Murry said.
“The long-term goal is to get the heart to heal by muscle regeneration instead of forming scar tissue after a patient has a heart attack,” he said.
Although the monkeys showed no adverse symptoms relating to the transplant, the scientists did detect an irregular heartbeat within two to three weeks following the transplant, which later disappeared as the transplanted cells became more electrically stable, they said.
Despite this, the results open the way for human clinical trials within the next few years, said Michael Laflamme, professor of pathology at Washington University.
“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,” Professor Laflamme said.
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