How to mend a broken heart

By Nikita Ved

Most organs have the capacity to regenerate to a certain degree following injury, unlike the heart which is the least regenerative organ in the human body. It is therefore unsurprising that heart disease is one of the greatest causes of morbidity and mortality, claiming more lives than any other disease worldwide.

The goal has always been to encourage the heart to heal rather than scar so that it still retains its function, with most focus on healing through cardiac muscle regeneration. This is no trivial pursuit. From preparation of the correct type of cell to integration of the cell into the target tissue, the process is fraught with potential pitfalls.

A recent study published in Nature Biotechnology made a huge leap towards fulfilling this aim. Liu and colleagues earlier this year sought to understand whether cardiac muscle cells made from human stem cells, also known as human embryonic stem-cell derived cardiomyocytes (hESC-CMs) could remuscularise and improve cardiac function in non-human primates with large myocardial infarctions (heart attack). Nine macaques were subject to myocardial infarction, as shown in figure 1, injected with either a vehicle (placebo) or hESC-CMs and followed up using magnetic resonance imaging (MRI). Observers noted that of those macaques injected with the hESC-CMs, the infarcted hearts were able to eject more blood than those treated with vehicle. This continually improved over 3 months, whereas vehicle-treated macaques showed a steady decline in function. Many of these hESC-CM-treated macaques also showed increased thickening of the infarcted heart muscle, indicating that the hESC-CMs were not only able to integrate into the damaged heart, but also enhance function.

Although this evidence is encouraging, it must be noted that this and many other studies involving experimental grafts cause spontaneous arrhythmias, where the cardiac rhythm is disrupted. Heart rhythms were measured using electrocardiograms (EKG) and whilst arrhythmias were observed in the hESC-CM-treated macaques, they were no more frequent or severe than those treated with vehicle. Another caveat often present in stem cell derived therapies is tumour formation at the cell injection site. Interestingly, no tumours were observed in those treated with hESC-CMs.

By using heart cells derived from human stem cells and injecting them into animals so closely related to humans, Liu and colleagues have made a great advancement in understanding how to best treat a heart attack.