Duchenne dystrophic muscle develops lesions in long‐term coculture with mouse spinal cord

When strips of human skeletal muscle from biopsies of normal children and donors with Duchenne muscular dystrophy (DMD) are explanted in organotypic coculture with fetal mouse spinal cord, many regenerating muscle fibers develop, become innervated, and maintain a remarkable degree of mature structure and function for more than 3–6 months in vitro. Sequential light microscopy in correlation with electron‐microscopic and electrophysiologic analyses showed that despite cross‐species innervation, these human muscle fibers develop stable cross‐striations, peripherally positioned myonuclei, and mature, functional motor endplates. Of special interest is the onset of significant progressive abnormalities, e.g., unusual focal myofibrillar lesions, in substantial numbers of innervated mature DMD muscle fibers after 2–4 months in culture. The focal myofibrillar lesions were not detected in normal muscle fibers maintained as long as 6 months in coculture, nor are they comparable to the generalized loss of cross‐striations observed in muscle atrophy following in vitro denervation of mature DMD fibers.