Stem cells and plasticity of skeletal muscle cell differentiation: potential application to cell therapy for degenerative muscular diseases

Abstract

Degenerative muscular diseases, such as muscular dystrophies, have been the representative targets of regenerative cell therapy. Although satellite cells play central roles in skeletal muscle regeneration that intrinsically occurs after muscle injury, their application to cell therapy is confronted by difficulties. Other stem cells expected to be applicable to cell therapy include muscle-resident stem cells and nonmuscle-resident stem cells. Moreover, dedifferentiated cells of skeletal muscle might provide unique system for cell therapy. Terminally differentiated myotubes have plasticity of differentiation and dedifferentiate under certain experimental conditions, including the expression of SV40 large T antigen or the homeobox gene Msx1. The dedifferentiated cells exhibit multipotency to transdifferentiate into multiple mesenchymal origin cells. In addition, fibroblasts or undifferentiated myoblasts treated with a drug acquire multipotency. These cells may open new doors in cell therapy.