Cardiac differentiation and hormonal regulation of human embryonic stem cells

摘要

Here we report on our progress in the generation of cardiomyocytes derived from human embryonic stem (hES) cells as well as their electrophysiological characterization. To improve our understanding of hES cells as a source for cellular cardiomyopasty, we performed patch-clamp recordings of action potentials (APs), mapping of excitation generation based on extracellular field potentials (FP) as well as drug screening for responses to hormones and neurotransmitters of the vegetative nervous system. AP measurements revealed nodal-like, atrial-like and ventricular-like AP morphologies. High resolution FP mapping applying micro electrode arrays (MEAs) identified predominant pacemaker areas in cardiac hES cell clusters. Application of the adrenergic agonist +-isoproterenol (Iso) and the muscarinic agonist carbachol (CCh) evoked enhancement and transient decrease of FP frequency, respectively. Moreover and in contrast to CCh, Iso dose-dependently increased voltage dependent Ca~(2+) channel (VDCC) activity independent of frequency regulation. Our data indicate that hES cells exhibit the full range of cardiac differentiation and a physiological response to the major transmitters of the vegetative nervous system. Therefore, they might serve as an ideal candidate for the use in cell replacement strategies.