Derivation and Utility of Cardiomyocytes from Human Pluripotent Stem Cells

Chris Denning

Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM),
Centre for Biomolecular Science,s University of Nottingham, NG7 2RD, UK

Abstract

We have demonstrated that functional cardiomyocytes can be derived from human embryonic stem cells, potentially offering a novel cell source for drug screening, disease modeling and cell replacement. However, before these goals can be realized, several issues must be tackled. We have sought to standardize feeder-free culture methods function in 14 hESC lines derived in 5 different countries, impacting on the ability to improve downstream technologies. Thus, we have demonstrated industrial scale automation of hESC culture to meet demands of commerce. Standardized culture also provides a platform from which differentiation to the cardiac lineage can be improved and directed. Moreover, high efficiency genetic modification has been demonstrated in 11 hESC lines, potentially providing new routes to RNAi library screening for genome analysis. We have also generated transgenic hESC lines that express puromycin N-acetyltransferase from the cardiac specific MYH6 promoter, allowing enrichment of cardiomyocytes to close to 100% purity by incubation with the antibiotic puromycin. This set of technologies is now being applied to proof of principle studies in drug screening and engineering in vitro disease models produced either by genetic modification or by exploitation of induced pluripotency (iPS) technology.