Skeletal Myoblasts for Heart Regeneration and Repair: State of the Art and Perspectives on the Mechanisms for Functional Cardiac Benefits

L.      Formigli; S.      Zecchi-Orlandini; E.      Meacci; D.      Bani

Abstract

Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cellbased therapy for cardiac repair and regeneration. Although SkMB engraftment into the postinfarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for postischemic cardiac dysfunction.

Keywords: Skeletal myoblast, cardiac regeneration, paracrine factors, sphingosine-1-phosphate, relaxin

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