Guest Lecture Chris Denning

Investigating cardiovascular disease with stem cell derived cardiomyocytes

Professor Chris Denning, Dept of Stem Cells, Tissue Engineering & Modelling (STEM), Centre for Biomolecular Sciences, University of Nottingham, UK
 

Cardiovascular diseases are a dominant cause of death in the developed world and new ways to understand the underlying cellular, molecular and functional mechanisms are needed. Novel opportunities to address this need have arisen from the ability to produce cardiomyocytes from human pluripotent stem cells (hPSCs), which comprise human embryonic and human induced pluripotent stem cells (hESC / hiPSC). Here, we will discuss our work towards in vitro modelling of genetic diseases that affect the electrophysiology of the heart (e.g. Long QT Syndrome) or structure and survival disorders (e.g. Duchenne muscular dystrophy). Notably, electrophysiological and pharmacological responses observed in the in vitro models accurately replicate known patient outcomes. We also find that these in vitro models are useful in evaluating the utility of genetic-based corrective therapies. Such observations go some way to validating hPSC models as a useful screening and development tool for drug and genetic therapy. Similarly, studies have shown these hPSC-cardiomyocytes offer real potential in drug safety assessment, providing novel ways to address an issue that has placed a socio-economic burden on the pharmaceutical for several decades. Finally, we will summarise our work towards automating hPSC culture and differentiation to provide high content screening opportunities for industry.