May 1, 2014  Print

A physician-scientist at Sydney’s Westmead Millennium Institute for Medical Research (WMI) has, in a world first, collaborated with scientists at the University of Washington to successfully grow heart muscle cells in sufficient quantity to repair the damaged heart of a primate after myocardial infarction (a.k.a. heart attack).

The significant breakthrough, published today in the prestigious scientific journal Nature, is being described as a “bold new step” towards solving the growing epidemic of chronic heart failure, which kills more than 20,000 Australians each year.

The paper’s first author, Westmead Hospital Cardiologist and WMI/University of Sydney Researcher Dr James Chong, collaborated with researchers from the University of Washington to produce the breakthrough findings.

For the first time they were able to grow stem cell-derived heart muscle at a sufficiently large scale to treat large animals.

Injecting the cells into the animals’ infarcted hearts resulted in large-scale re-muscularisation and regeneration of the failing organ.

Dr Chong said the research is a significant breakthrough in using the new technology of regenerative medicine for human patients with heart disease, at a time when the problem is growing.

“Chronic heart disease rates in Australia and worldwide are reaching epidemic proportions and one in two people with advanced-stage heart failure will die within one year of diagnosis,” Dr Chong said.

“While adult stem cells are already being used in clinical trials on heart attack sufferers, that method has so far demonstrated only modest benefits so new treatments are urgently needed.

“By using pluripotent stem cells, which have superior plasticity, we were able to grow and graft stem cell-derived heart muscle in significantly larger numbers than previously possible.
“We found that the stem cell-derived heart muscle engrafted and survived in the infracted hearts over a much longer period than has ever been previously demonstrated in a clinically relevant model.”

Dr Chong said this technology is getting closer to growing heart muscle cells on a scale large enough to treat human patients.

“This technology brings us one step closer to the clinic and a possible future cure for heart failure,” he said.

Working with Professor Charles Murry and his US team, Dr Chong showed that Human Stem Cell-Derived Heart Muscle (hESC-CM) grafts could be produced on a clinical scale and then cryo-preserved with good viability in preparation for transplantation.

Animal subjects, who had undergone conditions similar to a heart attack, were treated with hESC-CMs injected into the damaged heart tissue.

The subjects were observed for as long as three months – a much longer period than previous large animal studies – and results found that the new heart muscle cells achieved electro-mechanical coupling with the original host heart.

Furthermore, the study showed for the first time that in-growth of blood vessels from the host heart was responsible for supplying the grafted heart muscle with nutrients.
“The stem cell-derived heart muscle was able to replace damaged and dead heart tissue by up to 40 per cent,” Dr Chong said.

“These studies support the further use of human stem cell-derived heart muscle for heart regeneration which could one day be a cure for heart failure and replace the need for heart transplantation.”

University of Sydney Clinical Professor of Cardiology, Professor David Ross, said the work of Dr Chong and fellow researchers was an important step in possible new treatments for
heart failure.

“Heart muscle has little or no capacity for regeneration after damage and repeated insults result in progressive reduction in the heart’s pumping capacity, causing heart failure,” Professor Ross said.

“Current treatments have limited efficacy and do not rectify the basic problem of insufficient contractile heart muscle.

“The research in this paper suggests it is possible to insert functional new heart muscle in damaged areas in a primate heart very similar to a human heart.

“While more research is needed into the long-term efficacy and safety of this approach, if it proves effective it will transform the treatment of heart failure,” he said.

Dr Chong and a team at WMI are seeking additional funding in order to continue large animal modelling tests at Westmead in the hope of moving to human clinical trials in a few years.

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