Developing human iPSC-derived engineered atrial tissue for mechanistic study of atrial fibrillation and novel therapy development (Mr Alexander Grassam-Rowe)

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia in clinical practice and represents a significant disease burden worldwide.

The development of novel therapies, such as through tailored treatment of the underlying pathophysiology of AF, is urgently needed. For achieving such a goal, suitable model systems close to human tissue are required.

We recently established a novel method to generate human induced pluripotent stem cell (hiPSC) derived atrial myocytes (hiPSCs-AMs) showing mature atrial myocyte characteristics, improving on those reported by others.

The current proposal aims to further develop human iPSC-derived engineered atrial tissue (hiPSC-eAT) that provides a robust system for modelling human atrial fibrillation for mechanistic research and development of novel therapies.

Three integrated studies are planned: 1) hiPSC-eAT development; 2) development and characterisation of AF models based on A) hiPSC-eAT, utilizing hiPSCs from healthy subjects co-cultured with human myofibroblasts in engineered sheets mimicking the human atrial in vivo environment, and B) hiPSC-eAT derived from catecholaminergic polymorphic ventricular tachycardia (CPVT) subjects; with novel therapeutic strategy exploration in our hiPSC-eAt models; and 3) mathematical modelling of AF and in silico drug screening.

The project combines innovative technologies from biosynthetic material development, stem cells technology, optogenetics, optical imaging and mathematic modelling.