Skeletal muscle regeneration and plasticity of grafts

The sequence of molecular and cellular events of muscle ontogeny leads to the proliferation, fusion, and differentiation of myoblasts to muscle cells. This sequence is closely paralleled in the grafting-ischemia model in which adult myoblast-satellite cells function as the muscle precursor cells. The study of skeletal muscle regeneration is a fertile and promising area of research in myogenesis. The early regenerative development and maturation of muscle is similar regardless of the perturbation that induced the degeneration-regeneration sequelae. In light of this, we maintain that the skeletal muscle graft model is useful to rigorously evaluate many regulatory aspects of skeletal muscle development and maturation in an adult animal host. One advantage of the graft model is that manipulation of the adult host, such as with exercise or hormone treatment, allows insight into their regulatory roles in muscle development and maturation. These approaches are often not possible for developing skeletal muscle in utero or in ovo. After skeletal muscle grafting, many structural and functional characteristics change with time until they reach a stable value. Successful regeneration requires revascularization, cellular infiltration, phagocytosis of necrotic muscle fibers, proliferation and fusion of muscle precursor cells, reinnervation, and recruitment and loading. The time taken to reach stable values varies among different structural and functional variables, and many reach stable values that are less than those of control skeletal muscle. There are differences in the degree of regenerative success because of the size of muscle mass grafted. In small and large grafts, regeneration is enhanced by facilitation of the reinnervation. Regeneration is evident without vascular repair in grafts of up to approximately 6 g, although in all but the 100 to 150-mg grafts in rats, a significant necrotic core is present. Regeneration is typically unsuccessful when muscle masses greater than 6 g are grafted without vascular repair. Large muscles can be grafted with vascular repair, and in this case, the cellular response is quite different, as the majority of fibers survive rather than degenerate and regenerate. Changing the components of physical activity during skeletal muscle regeneration can alter several attributes of the graft phenotype. The consensus of several experiments supports the interpretation that proper recruitment and force development by grafts are essential variables in the regulation of the development and maturation of muscle grafts. Morphological and physiological attributes of grafts adapt to changes in the habitual level of physical activity in a qualitatively similar fashion to control muscle.(ABSTRACT TRUNCATED AT 400 WORDS)