Impact

There are currently no targeted therapies to treat heart failure. As such, 50% of patients will die in 5 years without a transplant. Post-transplantation includes life long immunosuppression which increases the risk of cancer and renal failure. There is a strong need for alternative therapies for heart failure, which would ideally prevent or even delay the need for a transplant. Our research using stem cell models from patients with heart failure allows us to visualise how mutations in genes associated with the sarcomere lead to a change in tissue structure and function. Disease modelling in 3D cardiac organoids provides a more accurate and non invasive way to model what is going on in a patients heart during disease.

reNEW research

We have generated more than 5 human stem cell lines from patients with forms of heart failure caused by mutations in several key genes. We have performed characterisation of these lines to assess the gene networks which are altered in disease, to assess changes in contractile function and visualise how these mutations result in remodelling of the sarcomere. Based on these findings, we plan to screen small molecules using these human stem cell models to look for new therapies to treat heart failure.

Image description

This image shows the sarcomeres of a human pluripotent stem cell differentiated line from a patient with dilated cardiomyopathy, which is one of the most common causes of heart failure and transplantation. Similar to a highway, sarcomeres form networks that spread through heart tissue. The cardiomyocyte specific protein TNNT2 is shown in red. TTN, a major structural and signalling protein in the sarcomere, is shown in white.

Credits

Hayley Pointer, Research Assistant, Heart Regeneration and Disease Lab, reNEW Melbourne.
Dr Kevin Watt, Team Leader, Heart Regeneration and Disease Laboratory, reNEW Melbourne.