Hypoxic preconditioning-engineered bone marrow mesenchymal stem cell-derived exosomes promote muscle satellite cell activation and skeletal muscle regeneration via the miR-210-3p/KLF7 mechanism

Sarcopenia is a gradual and widespread decline in muscle mass and function in skeletal muscle, leading to significant implications for individuals and society. Currently, there is a lack of effective treatment methods for sarcopenia. Muscle satellite cells(SCs) play a crucial role in the occurrence and development of sarcopenia, and their proliferation and differentiation abilities are closely related to the progression of disease. This study evaluated the effects of exosomes derived from hypoxic preconditioning bone marrow mesenchymal stem cells (BMSCs) on the proliferation of SCs and skeletal muscle regeneration. We found that the capacity for the proliferation and differentiation of SCs in elderly rats was notably diminished, leading us to create a sarcopenia model in elderly rats. By separating and extracting exosomes from BMSCs treated with normoxic (N-Exos) and hypoxic (H-Exos) conditions, in vivo and in vitro studies showed that both N-Exos and H-Exos can regulate the proliferation and differentiation of SCs in elderly rats, and promote skeletal muscle regeneration and functional recovery. The beneficial effects of H-Exos were also more significant than those of the N-Exos group. In vitro studies demonstrated that H-Exos could influence the expression of the KLF7 gene and protein in SCs by delivering miR-210-3P. This, in turn, impacted the phosphorylation of the PI3K/AKT signaling pathway and contributed to the function of SCs. H-Exos stimulated SCs and promoted skeletal muscle regeneration during sarcopenia by delivering miR-210-3P to target the KLF7/PI3K/AKT signaling pathway. This may serve as a possible treatment option for sarcopenia.