Pacemaker biologico : cellule staminali embrionali murine vs. cellule staminali cardiache adulte

Recent progress in stem cell research makes it possible to use them in cardiac therapy. Our aim was to characterize the pacemaker current (If) and HCN channels distribution in murine embryonic stem cells and cardiac adult mesoangioblasts following differentiation towards a pacemaker-like phenotype. Mouse embryonic stem cells (mESCs) are pluripotent stem cells and they were differentiated through formation of embryoid bodies (EBs). A fraction of these cells exhibited action potentials characterized by a slow diastolic depolarization typical of pacemaker myocytes and expressed the If current. Immunofluorescence analysis revealed that both the HCN1 and HCN4 isoforms of the pacemaker channel are expressed. Rhythmic cells responded to β-adrenergic and muscarinic agonists: isoproterenol accelerated and acetylcholine slowed spontaneous rate. Accordingly, β1- and β2-adrenergic, and M2-muscarinic receptors were detected by immunofluorescence. Cardiac mesoangioblasts are vessel-associated clonogenic, self-renewing progenitor cells identified in the post-natal murine heart, which can be induced to differentiate into cardiac myocytes. A subpopulation of cardiac mesoangioblasts induced to differentiate in vitro into cardiomyocytes acquires a phenotype with specific pacemaker cells properties, such as the presence of If current and the expression of the HCN4 isoform of pacemaker channels. As in native cardiac pacemaker cells, f-channel modulation by autonomic transmitters, in these cells, contributes to control of spontaneous rate. These results show that both of these cell types express proteins which underlie generation and modulation of heart rhythm, and can represent a potential substrate for a biological pacemaker.