Boosting the long-term effectiveness of heart cell therapy

Targeting the Hippo pathway to enhance the regenerative capacity of iPS-derived cardiomyocyte

Adult heart cells have a limited ability to regenerate and are often replaced with scar tissue after damage such as a heart attack. This affects the heart’s ability to pump blood around the body and can eventually lead to heart failure. A promising solution to this is ‘heart cell therapy’ where heart cells grown in the lab are implanted to replace the damaged tissue. However, it’s hard to keep implanted cells alive and healthy once they are in the heart, where the surrounding conditions are much more challenging than life in a test tube. Dr Oceandy and his team have evidence that an important series of signals in heart regeneration, called the Hippo pathway, could help. In this study, they will look at whether increasing the activity of the Hippo pathway can boost the survival of heart cells once they’ve been implanted. They think that switching on a molecule called YAP, which activates the Hippo pathway, will boost the ability of the implanted heart cells to induce regeneration of the heart in mice who have had a heart attack. If successful, they will test whether switching on YAP via another molecule (5-HT2B) can reproduce these effects. This is important because it’s easier to target 5-HT2B with drugs than YAP or other parts of the Hippo pathway. In fact, several 5-HT2B drugs already exist and could be used as potential treatments to support heart cell therapy, providing effective long-term treatment for heart attacks.