Regulation of muscle stem cells activation: the role of growth factors and extracellular matrix

Abstract

Vertebrate skeletal muscle is composed of organized multinucleate muscle fibers and also various subpopulations of cells localized in between. Some of them can be considered as the stem cells, however, few of them are able to follow myogenic program. First and most extensively studied so far, are the satellite cells that serve as tissue-specific precursors for muscle growth and repair. They are located between the basal membrane and the sarcolemma of adult muscle myofibers. They remain quiescent but can be activated in response to muscle damage resulted from mechanical injury, stretching, exercise, denervation, or progressing muscle dystrophy. Except the satellite cells also other stem cells could participate in muscle fibers reconstruction. Such cells as pericytes and mesangioblasts, muscle-derived stem cells, including so-called muscle side population, or CD133 expressing cells, were proved to be able to undergo myogenic differentiation in experiments involving their in vitro coculture with myoblasts or transplantation to injured skeletal muscle. In the current review, we will summarize stimuli influencing skeletal muscle stem cells activation, that is, growth factors which are secreted by muscle fibers, satellite cells, inflammatory cells, or released from basal lamina. We will also describe factors present within the skeletal muscle niche which interactions with stem cells lead to their activation, proliferation, asymmetric divisions, migration, and finally differentiation into myotubes, and then terminally differentiated myofibers.