Résumé :
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Adult stem cells can be isolated from skeletal muscle and display spontanous multi-lineage differentiation including towards cardiac lineage. (Arsic et al. 2008)*. Before differentiation and in addition to Sca-1 and Bcrp1/ABCG2, skeletal Muscle-Derived Stem Cells (skMDSC) express the pluripotency markers Sox2, Lin28 and Nanog and the cardiac progenitor marker Islet1, but do not express Oct4. Detailed analysis of skMDSC differentiation shows the appearance of autonomously pulsing cells that sustain a beating phenotype for over 2 months in culture. In addition to their autonomous rhythm, these differentiated cells harbour all the features of true pacemaker cells, specialized cardiac cells from the sinoatrial node responsible for initiating and maintaining the cardiac rhythm. These typical properties of pacemaker cells include spindle-like elongated morphology, expression of HCN4 (hyperpolarisation-activated cAMP-gated potassium channel 4), connexin45 and Cav1.3 (alpha1D) calcium channel as well as cardiac Troponin I and a-actinin contractile proteins. SkMDSC differentiated into beating cardiomyocytes also display the electrophysiological signature of pacemaker cells in particular Calcium transients and response to b-adrenergic stimulation. In vivo, I.V. transplantation of EGFP-expressing wild type skMDSC into mice knocked-out for both Cav1.3 and Cav3.1 and presenting with severe arrhythmia and bradycardia resulted in significant increase of their mean heart rhythm and reduced arrhythmia within 10 days after transplantation, an effect correlated with the nesting of EGFP positive cells in the sinoatrial node of recipient mice.The presence in human muscle of similar progenitor cells capable of differentiating into pacemaker cells should provide a powerful alternative to genetically modified mesenchymal stem cells or IPs-derived cardiac cells for biological pacemaking and cardiac repair through autologous cell transplantation.*Arsic, N, Mamaeva, D, Lamb, N. and Fernandez A. (2008) Muscle-Derived Stem Cells isolated as Non-Adherent Population give rise to Cardiac, Skeletal Muscle and Neural Lineages. Experimental Cell Research, 314(6):1266-80.
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