Electrophysiological properties of stem cells

摘要

New concepts for treatment of myocardial infarction include the implantation of adult stem cells for regeneration of damaged muscle tissue. Several clinical trials have demonstrated a small, but significant improvement of ventricular function. Transdifferentiation of stem cells into cardiomyocytes, formation of new vessels and paracrine factors have been discussed as putative mechanisms for the therapeutic effect. Several types of stem cells have been used clinically including myoblasts derived from skeletal muscle satellite cells, bone marrow-derived stem cells or blood-derived mononuclear progenitor cells. In addition, multiple organs were shown to contain a small number of stem cells that could differentiate into cardiomyocytes.Embryonic stem cells differentiate into spontaneously beating cells that have varying electrophysiological properties. Their action potentials resemble those of cardiac pacemaker cell, atrial or ventricular myocytes (Figure 1) suggesting true differentiation into cardiomyocytes. Beating cells derived from a newly described population of skeletal muscle-derived cells ("skeletal precursors of cardiomyocytes" [SPOCs]) also exhibit spontaneous action potentials, however, unlike cardiac pacemaker cells, their electrical activity is suppressed with the sodium channel blocker tetrodotoxin (Figure 2). Undifferentiated bone marrow-derived mesenchymal stem cells are not electrically excitable. Nevertheless, they express functional ion channels like L-type Ca(2+) channels, albeit not in every cell. Co-culturing stem cells with neonatal rat ventricular myocytes induces good electrical contacts between cells via gap junction formation. Excitatory wave fronts spread evenly in the co-culture. By contrast, gap junctions fail to form when myoblasts are co-cultured with neonatal cardiomyocytes and reentry arrhythmias develop. This pathomechanism could serve as an explanation for the enhanced clinical risk of arrhythmia after transplantation of myoblasts into the infarcted hearts.