The regeneration process of the striated urethral sphincter involves activation of intrinsic satellite cells

Abstract

The regeneration of adult skeletal muscle is mediated by satellite cells. Classically, these are considered to be somitically derived cells that colonize the limbs during early embryogenesis. The striated urethral sphincter presents specific developmental characteristics that distinguish it from skeletal muscles, such as the non-somitic origin of its precursor cells and the late formation of its myofibers. This prompted us to determine whether the striated urethral sphincter can regenerate after injury by the same mechanism as skeletal muscles. By means of the single myofiber explant culture technique we investigated the presence of satellite cells in the striated urethral sphincter of male mice and evaluated their ability to recapitulate a myogenic program. In addition, a myotoxic substance (notexin) was injected into the sphincter in order to provoke rapid destruction of the myofibers; the regeneration process was studied by means of electrophysiological and histological techniques. Satellite cells expressing pax7 were found attached to the sphincteric myofibers. They proliferated and expressed MyoD, Myf5 and desmin after 2 days in culture. After 10 days, they formed multinucleated myotubes expressing alpha-actinin-2. In vivo, complete recovery of the striated urethral sphincter, as assessed by normalization of muscle strength and of myofiber number and diameter, was observed after 3 weeks, and resulted from the fusion of myogenic cells. These results demonstrate that the striated urethral sphincter can regenerate by means of a myogenic program involving intrinsic satellite cells. The therapeutic implications of this knowledge and the possible origin of the sphincteric satellite cells are discussed.