International immunopharmacologySep 22, 2024

Exosomes from low-oxygen-treated bone marrow stem cells help activate muscle stem cells and support muscle repair through the miR-210-3p/KLF7 pathway

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 27, 2026

Abstract

Exosomes from hypoxic preconditioning bone marrow mesenchymal stem cells significantly enhance skeletal muscle regeneration in elderly rats.

Elderly rats exhibited reduced ability for satellite cell proliferation and differentiation, indicative of sarcopenia.
Both normoxic and hypoxic exosomes were found to regulate satellite cell activity and promote muscle recovery.
Hypoxic exosomes showed more pronounced benefits compared to normoxic exosomes in muscle regeneration.
Hypoxic exosomes influenced the KLF7 gene and protein expression in satellite cells through the delivery of miR-210-3P.
The activation of the PI3K/AKT signaling pathway was linked to the function of satellite cells stimulated by hypoxic exosomes.

Simplified

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.

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Exosomes from low-oxygen-treated bone marrow stem cells help activate muscle stem cells and support muscle repair through the miR-210-3p/KLF7 pathway

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