Several diseases impair skeletal muscle function, significantly reducing the quality of life by diminishing muscular capability. Stem cell therapy with muscle stem cells (MuSCs) offers a promising solution as these cells can fuse with damaged myotubes to improve muscle regeneration and allow genetic complementation. However, quiescent MuSCs are a small fraction of skeletal muscle cells and cannot be expanded in vitro because they become activated upon isolation. In our laboratory, we have developed a protocol to expand human myoblasts, which upon differentiation give rise to, quiescent muscle reserve cells (MuRCs). MuRCs are very similar to MuSCs but with the advantage that they can be produced in large numbers in vitro and have shown good regenerative potential in mice. Better characterization of these cells is therefore crucial for potential therapeutic applications.

In our study, we first established that a small proportion of MuRCs express the chemokine receptor CXCR4, which is known to be involved in cell migration. We then investigated the myogenic characteristics of CXCR4+ and CXCR4- MuRCs by isolating them by fluorescence- activated cell sorting (FACS). We also showed that the proportion of CXCR4+ MuRCs was increased by the use of platelet-rich plasma (PRP) in the culture medium. Furthermore, we demonstrated that activation of the AMP-activated protein kinase (AMPK) pathway leads to an increased expression of the transcription factor Pax7 in MuRCs without affecting their myogenic differentiation. These findings suggest that optimizing CXCR4 expression and exploiting the AMPK pathway may enhance the regenerative capacity of MuRCs, making them a viable option for stem cell therapy in muscle repair.