Biomedical engineers at Duke University have created a fully functioning artificial human heart muscle large enough to patch over damage typically seen in patients who have suffered a heart attack. The advance takes a major step toward the end goal of repairing dead heart muscle in human patients.
The study appears online in Nature Communications.
‘Right now, virtually all existing therapies are aimed at reducing the symptoms from the damage that’s already been done to the heart, but no approaches have been able to replace the muscle that’s lost, because once it’s dead, it does not grow back on its own,’ said Ilya Shadrin, a biomedical engineering doctoral student at Duke University and first author on the study.
‘This is a way that we could replace lost muscle with tissue made outside the body.’
Unlike some human organs, the heart cannot regenerate itself after a heart attack. The dead muscle is often replaced by scar tissue that can no longer transmit electrical signals or contract, both of which are necessary for smooth and forceful heartbeats.
The end result is a disease commonly referred to as heart failure that affects over 12 million patients worldwide. New therapies, such as the one being developed by Shadrin and his advisor Nenad Bursac, Professor of Biomedical Engineering at Duke, are needed to prevent heart failure and its lethal complications.
Current clinical trials are testing the tactic of injecting stem cells derived from bone marrow, blood or the heart itself directly into the affected site in an attempt to replenish some of the damaged muscle. While there do seem to be some positive effects from these treatments, their mechanisms are not fully understood. Fewer than one per cent of the injected cells survive and remain in the heart, and even fewer become cardiac muscle cells.
Heart patches, on the other hand, could conceivably be implanted over the dead muscle and remain active for a long time, providing more strength for contractions and a smooth path for the heart’s electrical signals to travel through. These patches also secrete enzymes and growth factors that could help recovery of damaged tissue that hasn’t yet died.
For this approach to work, however, a heart patch must be large enough to cover the affected tissue. It must also be just as strong and electrically active as the native heart tissue, or else the discrepancy could cause deadly arrhythmias. This is the first human heart patch to meet both criteria.
‘Creating individual cardiac muscle cells is pretty commonplace, but people have been focused on growing miniature tissues for drug development,’ said Bursac.
‘Scaling it up to this size is something that has never been done and it required a lot of engineering ingenuity.’
The cells for the heart patch are grown from human pluripotent stem cells – the cells that can become any type of cell in the body. Bursac and Shadrin have successfully made patches using many different lines of human stem cells, including those derived from embryos and those artificially forced or ‘induced’ into their pluripotent state.