Stem cell breakthrough: repairing heart attack damage

New research led by the Westmead Institute for Medical Research (WIMR) has solved a complication that could occur following an experimental procedure to repair damaged heart muscle. The breakthrough comes 10 years after Professor James Chong first led a research team at WIMR that used stem cells to successfully grow new heart muscle, to repair damage caused by heart attack.

“At the moment, damaged or dead heart muscle cannot be replaced to any meaningful degree, so a heart transplant is the only ‘cure’ available to patients with end stage heart disease,” said Chong, who serves as Co-Director of WIMR’s Centre for Cardiac Research.

“So the potential to replace new, healthy heart muscle with a graft that has been created using stem cells could save many thousands of lives.”

Unfortunately, a potential complication was identified following a graft of this stem cell-derived heart muscle — ventricular arrhythmias. Ventricular arrhythmias cause the heart to beat too fast, which prevents oxygen-rich blood from circulating to the brain and body and may result in cardiac arrest.

The new research, conducted on animal models, shows that the type of stem cells used, and the way they are developed into new heart muscle, can be a cause of ventricular arrhythmia. The team’s results were published in the journal Nature Cardiovascular Research.

“We have detected specific cardiomyocytes (a type of heart muscle cell) that contribute to these ventricular arrhythmias, and we have been able to identify two unique surface marker signatures (SIRPA+/CD90-/CD200+ and SIRPA+/CD90-/CD200),” Chong said.

“This allows us to differentiate between arrhythmogenic and non-arrhythmogenic cardiomyocytes respectively, meaning we can choose the cells that are less likely to result in a deadly ventricular arrhythmia.”

In terms of treating ventricular arrhythmias, the research team has shown that a combination therapy of existing drugs can provide the required control. Chong explained, “When combined, amiodarone (a drug that works directly on heart tissue to slow the nerve impulses in the heart) and ivabradine (a drug used to treat heart failure by slowing the heart rate) were shown to significantly reduce the incidence of ventricular arrhythmia following this graft process.”

With planning and recruitment for human clinical trials of stem-cell derived heart muscle grafts currently underway around the world, including at Westmead, Chong said there is an urgent unmet need to understand why arrythmias occur, and to develop treatment strategies to control or prevent them.

“We are delighted that our research findings help to overcome a significant hurdle for the successful human application of stem cell-derived heart muscle grafts,” he said.

Image credit: iStock.com/Sewcream