Using 3D heart tissue models to find out what controls the severity of ARVC

Creating 3D models of ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) disease with light-induced tuneable severity in stem cell-derived cardiomyocytes

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease. In ARVC, heart muscle cells – cardiomyocytes – often do not stick together properly because of one or more genetic mutations that affect cell to cell adhesion. Cardiomyocytes die and are replaced with fatty scar tissue, preventing the heart from pumping blood properly and causing abnormal heart rhythms. Some people have a more severe manifestation of the disease, especially in early adulthood, and the reasons why are unknown. Dr Vinoj George at Keele University, will supervise a PhD student to create 3D heart tissue models that can be used to investigate the underlying molecular biology that causes the varying severity of ARVC. Dr George plans to introduce a genetic mutation that is associated with severe cases of ARVC into human stem cells, before turning them into mature cardiomyocytes grown on a 3D scaffold. By using optogenetic technology, where light is used to ‘fine-tune’ the molecular activity within cells, the team will create heart tissue models with varying degrees of ARVC severity. This approach will help them to identify the mechanisms that are responsible for giving rise to the wide spectrum of disease severity seen in individuals with ARVC. New knowledge obtained from these models could help us identify people at high risk of developing severe ARVC and inform us of new ways to combat the disease. Notes: humans or animals are not involved in this study.