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Cell transplantation is a successful strategy to obtain myocardial improvement. However, the mechanisms involved are unclear. We collaborate with the Cell Therapy group in an effort to understand the consequences of the co-existence of skeletal myoblasts and cardiomyocytes in vivo and in vitro . One study we have performed recently is the assessment of intracellular communication between skeletal and cardiac muscle cells. Gap junction formation between grafted skeletal myoblasts (SM) and host myocardium may be implicated with arrhythmias observed in clinical trials of SM transplantation and with possible cardiomyogenic transdifferentiation of grafted SM. However, the presence of such junctions remains controversial. We have studied the ability of SM to form electrical coupling with isolated adult rat ventricular myocytes (VM), and assess whether connexin43 (Cx43) overexpression could enhance gap junctional conductance. C2C12 myoblast lines stably overexpressing Cx43 were generated by gene transfection and clonal selection. Cx43 overexpression was confirmed by western blotting and immunofluorescence. VM were co-cultured with either SM overexpressing Cx43 (VM-Cx43) or control SM (VM-SM) in vitro . Using dual patch clamping, we found functional gap junctions between pairs of SM and VM. This was almost 40% higher when VM-Cx43 were used. We conclude that overexpression of Cx43 improves electrical coupling between SM and VM. The increased communication may represent a useful strategy for improving cell-cell communication for cell transplantation.
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