Abstract

Human Pluripotent Stem Cells In Cardiovascular Drug Discovery And Safety Pharamacology: Towards Precision Medicine

Christine Mummery, Professor of Developmental Biology, Chair Dept. of Anatomy & Embryology, Leiden University Medical Center

Derivation of many different cell types from human pluripotent stem cells (embryonic stem cells or HESCs and induced pluripotent stem cells or hiPS cells) is an area of growing interest both for potential cell therapy and as a platform for drug discovery and toxicity. Most particularly, the recent availability of methods to introduce specific disease mutations into human pluripotent stem cells and/or to derive these cells as hiPS cells by reprogramming from any patient of choice, are creating unprecedented opportunities to create disease models “in a dish” and study ways to treat it or slow down its rate of development. We have used these methods to produce isogenic pairs of hiPSC lines to compare diseased and corresponding control cardiomyocytes and vascular endothelial cells and identify disease related phenotypes and mechanisms. We have examined drug responses of hESC-derived cardiomyocytes to a variety of cardiac and non-cardiac drugs and shown that iPSC derived cardiomyocytes with mutations in ion channel genes can accurately predict changes in cardiac electrical properties and reveal drug sensitivities also observed in patients. Similar studies will be described using vascular endothelial cells from hPSC.