In a moderate injury the satellite cells use the basement membranes of necrotic fibers as a scaffold to ensure a similar position of the new muscle fibers. As a late step in muscle regeneration the basement membrane of the necrotic fiber is phagocytized. In muscular dystrophy the response to injury is different. The invasion of inflammatory cells is much greater and the basement membranes of necrotic muscle fibers are removed before they have had a chance to act as scaffolds for the generation of new muscle fibers and to guide innervation. The result is a muscle tissue with abnormal muscle fiber arrangement.
Fibrosis is a major obstacle to all types of gene therapy in muscle disease.
A schematic view of the involvement of fibrosis and muscle regeneration in the pathology of muscular dystrophy is shown in figure 3. Schematic illustration of the relationship between fibrosis and regeneration in a moderate muscle injury versus muscular dystrophy. In a healthy muscle, muscle fiber damage leads to a moderate activation of connective tissue cells. Satellite cells are activated and replace the damaged muscle with new muscle fibers. In a dystrophic muscle, the primary defect leads to continous myofiber degeneration which leads to massive activation of connective tissue cells, resulting in fibrosis.