LEUKEMIA INHIBITORY FACTOR TREATMENT STIMULATES MUSCLE REGENERATION IN THE MDX MOUSE

A number of growth factors are involved in coordinating muscle cell pr oliferation and differentiation, particularly after injury and in dise ase. Leukaemia inhibitory factor (LIF) strongly stimulates the prolife ration of myoblasts in vitro and in vivo and its expression in muscle after injury suggests that LIF may have a role as a trauma factor, The mdx mouse was used to study the effects of LIF on in vivo muscle rege neration during disease. The rationale for using trophic factors such as LIF to treat neuromuscular disease includes the understanding that these molecules show some degree of selectivity for the population of cells in which they are effective. LIF was administered to muscle of t he mdr mouse using osmotic pumps implanted subcutaneously in unrestrai ned mice. The growth factor was continuously delivered into the vastus lateralis muscle at 7 U/mu l for 7 days via a catheter. The results s how that LIF increased the rate of muscle regeneration in mdx mice by stimulating the formation of larger myotubes. LIF treatment also incre ased the number of regenerating myotubes in the perfused area. This my otrophic action indicates that LIF contributes to muscle regeneration. Together with its known neurotrophic action, LIF is a potential thera peutic agent for the treatment of neuromuscular disease.