Satellite Cell Proliferation: Starting Point and Key Steps to Regeneration and Cell-Mediated Gene Therapy

Regeneration of muscle fibres following injury requires the activation of quiescent satellite cells, their proliferation and finally their differentiation and fusion into multi-nucleated myotubes which will, after maturation, replace the damaged fibre. Although many reports have been published concerning the differentiation potential of satellite cells in vitro, and the formation of new fibres in vivo, very few studies have looked at their activation and their proliferation. In this study we report that myf-5, a member of the myogenic regulatory factors, is an early marker of the activated satellite cells. During regeneration in human muscle it is important to consider the proliferative capacity of the satellite cells since the proliferation of human somatic cells is limited. Although we show that the limit in proliferation should not interfere with regeneration in normal muscle, it is probably a limiting factor in cases of muscular dystrophy when the muscle will undergo repeated cycles of degeneration and regeneration. Another field where the limit in proliferation is crucial is cell-mediated genetherapy, since if satellite cells are to be used as vectors they must be amplified before introduction into the host. In this study we give a detailed evaluation of the proliferative capacity of human satellite cells at different ages, and describe a system which has been used to increase this capacity, using T antigen from SV40. The effect of the expression of T antigen in human satellite cells, and the general consequences of the limit in the proliferative capacity on both pathological situations and cell-mediated gene therapy are discussed.