Tissue Eng Regen Med.  2024 Apr;21(3):487-497. 10.1007/s13770-023-00618-w.

Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p

• Shin DI
• Jin YJ
• Noh S
• Yun HW
• Park DY
• Min BH

• KMID: 2554995
• DOI: http://doi.org/10.1007/s13770-023-00618-w

Abstract

BACKGROUND
Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilagederived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model.
METHODS
The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway.
RESULTS
F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and b-catenin.
CONCLUSION
F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Keyword

Sarcopenia; Fetal cartilage-derived progenitor cells; Exosomes; miR-145-5p; Wnt signaling pathway