Bone marrow-derived mesenchymal stromal cells and platelet rich plasma in skeletal muscle regeneration

Adult skeletal muscle is able to undergo regeneration after damage, thanks to satellite cells. However, in case of severe muscle damage, the efficiency of these cells cannot be sufficient to promote tissue repair [1]. Recent trends are attempting to identify strategies aimed to improve the endogenous muscle repair potential. The administration of bone marrow-derived mesenchymal stromal cells (BM-MSCs), thanks to their secretion of paracrine factors, displays promising clues in skeletal muscle healing [2]. However, some criticisms hamper their clinical application, namely scarce survival in the host tissue and the need to avoid animal serum contamination in manipulation. In this context, platelet rich plasma (PRP) offers several advantages. Indeed, PRP as a source of multiple growth factors could represent an optimal substitute for animal serum in vitro and could provide beneficial therapeutic effects in vivo in the tissue injury site. However, controversial clinical findings exist for its therapeutic application in skeletal muscle injuries [3]. In this study we evaluated: i) the effect of PRP on both C2C12 myoblasts and BM-MSCs in term of viability, survival, proliferation and myogenic differentiation and ii) the effect of PRP in combination with BM-MSCs in sustaining and promoting myogenic differentiation. We found that PRP was able to induce an increase of C2C12 and MSCs survival, viability and proliferation, EdU incorporation, Ki67 expression and and activation of Akt and Notch-1 signalling. PRP was also able to promote C2C12 myoblast differentiation as evaluated by the analysis of myo-d, myogenin, and α-sarcomeric actin expression. Finally, the co-colture C2C12 / BM-MSCs in the presence of PRP showed an increase of all parameters of survival, proliferation and differentiation as compared to PRP treatment alone. In conclusion, our data suggest that the combined use of PRP and BM-MSC can be considered as a valuable tool in in the field of skeletal muscle regenerative medicine. References [1] Costamagna et al. (2015) Adult Stem Cells and Skeletal Muscle Regeneration.Curr Gene Ther,15:348 [2] Sassoli C et al.(2014) Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P) exerts a stimulatory effect on skeletal myoblast proliferation. PLoS One. 29:108662 [3] Andia I, Abate M. (2015) Platelet-rich plasma in the treatment of skeletal muscle injuries. Expert Opin Biol Ther;15:987