Principal Investigators
Professor Chris Denning ,University of Nottingham
Professor Lior Gepstein, Technion – Israel Institute of Technology
Overview
Cardiovascular disease is the leading cause of death worldwide and around 175,000 people suffer heart attacks each year in the UK each year. One of the most promising treatments for heart failure is to grow new heart muscles using stem cell technologies that can be transplanted into the heart and improve its pumping power.
In this project, Professor Denning and Professor Gepstein manipulated special stem cells, called human induced pluripotent stem cells, or hiPSCs, to study heart behaviour, particularly when heart function is harmed by severe genetic conditions such as hypertrophic cardiomyopathy. They then used powerful microscopes and computer algorithms to show that cells with the genetic mutation had disturbances in their beating rhythm, contraction and calcium functionality. Importantly, they were used to show that a combination of drugs that have previously tested in the clinic was successful in restoring normal heart rhythm.
In further studies, the researchers combined the hiPSC technology with the cutting-edge methodology, of Optogenetics, which uses light-sensitive proteins to modify the electrical properties of tissues with light, focusing primarily on the brain. They demonstrated the ability to use light to pace a tissue-engineered model of heart tissue comprised from hiPSC derived cardiac cells (optogenetic pacing) and to synchronize its beating pattern (optogenetic resynchronization therapy). Finally, they demonstrated the ability to generate a fast and irregular arrhythmia in the generated model and the ability to convert it to normal rhythm through light delivery (optogenetic defibrillation.)