Impaired muscle differentiation in explant cultures of Duchenne muscular dystrophy.

ABSTRACT

Muscle cultures were established from 11 normal controls and 13 Duchenne muscular dystrophy biopsies by an explant technique. Under light microscopy the most distinctive features of Duchenne muscular dystrophy cultures were an earlier migration and a delay or even an absence of fusion of mononucleated cells in comparison with the controls. Furthermore, most fusing dystrophic cells were morphologically different from conventional myoblasts, and, at a later stage, myotube formation was significantly reduced. In contrast to controls, dystrophic cultures displayed a total absence of spontaneous contractions and poor myofiber longevity. Atypical myogenic cells seen in Duchenne muscular dystrophy cultures differed ultrastructurally from normal myoblasts in having a smaller population of free ribosomes and polyribosomes, prominent rough endoplasmic reticulum, and abundant intermediate filaments. The dystrophic myofibers that had reached relative maturity always exhibited a poorly developed contractile apparatus in contrast to structurally well-defined normal myofibers. It is inferred that the impaired myogenesis observed in Duchenne muscular dystrophy cultures results primarily from defective fusion involving atypical myogenic cells.