(622l) Generation of Cardiac Cell Lineages from Human Pluripotent Stem Cells By Modulation of WNT Signaling Via Small Molecules

Bao, X., University of Wisconsin Madison

Human pluripotent stem cell (hPSC)-derived cardiomyocytes, endothelial cells and their progenitors are important tools for cardiovascular research and have significant therapeutic potentials. During the past 10 years, rapid methodological developments for creating de novo cardiac lineages have been made. However, most of these approaches require animal cells, fetal bovine serum, or various cytokines, limiting their application for large-scale cardiac lineage production for therapeutic applications. Here, we show that temporal Wnt signaling modulation is both necessary and sufficient for cardiomyocyte and endothelial cell specification from hPSCs under chemically-defined, albumin-free conditions. Firstly, we systematically optimized our previous GiWi protocol for cardiac differentiation, and found that RPMI basal medium alone is sufficient to support hPSC differentiation to cardiomyocytes with a purity of more than 90%. In addition, we developed a robust endothelial progenitor differentiation platform that uses a minimalistic medium, consisting of only DMEM and ascorbic acid, via modulation of canonical Wnt signaling pathway. These two fully defined platforms should facilitate large-scale production of xeno-free cardiomyocytes and endothelial cells respectively for both research and clinical applications.