Metabolic reprogramming as therapeutic strategy to ameliorate skeletal muscle tissue engineering procedures

Background: Stem cells and regenerative medicine raise great expectations because of the promise to reconstitute aged, injured and diseased tissues. While success has been achieved for hematological and epithelial diseases, several hur- dles remain for diseases affecting skeletal and cardiac muscle. Maximizing the sur- vival and the myogenic activity of the engrafted cells used for tissue engineering by preconditioning with suitable bioactive molecules would allow better therapeu- tic outcomes. Notably, energy management and metabolic reprogramming seem to play a key role in stem cell differentiation. We, therefore, propose that myogenic precursors preconditioning by metabolic shift induction might potentiate and ame- liorate the efficacy of reconstructive muscular tissue strategies. Methodology: We will evaluate the effect of metabolic reprogramming on stem cell myogenic capabilities and survival and on 3D artificial muscle generation in vitro and in vivo. Results: Our data show that TMZ exert a profound effect on stem cells, altering their gene expression profile. It stimulates differentiation of both C2C12 and satel- lite cells as shown by enhanced expression of muscle-specific genes and proteins and by higher myotube size and fusion index. Moreover we developed a biotech- nology demonstrating the possibility to build in vitro and in vivo a complete and functional artificial muscle in mice. Conclusions: We expect to select metabolic remodeling agents able to improve the generation and implantation of artificial muscles. We will also clarify the key metabolic changes occurring during muscle differentiation, and this will allow further specific therapeutic approaches for muscle replacement.