Does induction of CCAAT/Enhancer-Binding Protein β Expression With the Phosphodiesterase Inhibitor Isobutylmethylxanthine improve Myoblast Engraftment Into Dystrophic Muscle?
Duchenne muscular dystrophy is a genetic disorder for which no cure exists. One therapeutic approach is transplantation of myogenic progenitors to restore dystrophin to damaged muscle, but this approach is limited by poor engraftment of cultured myoblasts. Transient upregulation of CCAAT/enhancer-binding protein β in primary myoblasts using the phosphodiesterase isobutylmethylxanthine (IBMX) increases satellite cell marker expression in cultured myoblasts, improves their migration, and increases their survival after transplantation. When transplanted into C57BL/10ScSn-mdx/J mice , IBMX-treated myoblasts restored dystrophin expression and were able to occupy the satellite cell niche more efficiently than controls. A myoblast culture approach that reprograms myoblasts to a more primitive state, resulting in improved transplantation outcomes and reinvigorating research into myoblast transplantation as a viable therapeutic approach, is described.
The findings in this study reinforce the importance of appropriate pain management, keeping well babies with their mothers to remain together, 24 hours a day, and avoidance of non-medically indicated formula supplementation.