Abstract
Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution.
Highlights
Human embryonic stem cells are derived from the inner cell mass of human blastocysts or originate from morula stages of the embryo
Very few aggregates from both Human iPS cells (hiPSCs) and Human embryonic stem cells (hESCs) started beating on day 8 or day 9, most of the aggregates started beating at day 10
In this study we have analyzed the electrophysiological properties of cardiomyocytes derived from reprogrammed fibroblasts in comparison to cardiomyocytes derived from human embryonic stem cells
Summary
Human embryonic stem cells (hESCs) are derived from the inner cell mass of human blastocysts or originate from morula stages of the embryo. These cells have the ability to self-renew while maintaining their ability to differentiate into all cell types of the embryo, including cardiomyocytes [1,2]. HESC-CMs acted as biological pacemakers for the recipient myocardium after being transplanted into electrophysiologically silenced guinea pig and swine hearts [4,5]. It has been reported that hESC-CMs do express MHC class I molecule at low levels and expression increase upon differentiation in-vitro, and these cells will certainly evoke an immune response in the host after transplantation [7]
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