Metabolic Maturation Media Improves Physiological Function of Human iPSC-derived Cardiomyocytes

iPSC-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. In this study, we describe a maturation media (MM) designed to provide oxidative substrates adapted to the metabolic needs of hiPSC-CMs as compared to standard RPMI/B27 media. RNA sequencing was performed to gain insight into the underlying molecular basis for the changes. Compared to baseline (day 21) conditions, three weeks subsequent exposure to MM (day 41) caused a significant differential expression in genes. GO analysis of the MM-differentially upregulated genes were informative, mapping to mitochondrial metabolism. Additionally, multiple Ca2+ cycling/sarcoplasmic reticulum (SR), sarcomeric, and ion channel genes were differentially expressed. These gene expression changes indicated that supplementation with oxidative substrates and subsequent metabolic changes might affect cardiomyocyte electrophysiology, Ca2+ cycling and contractility. examination of gene expression changes after 3 weeks (day 41) of culture in either RPMI or MM media (compared to baseline, day 20 iPSC-CMs)