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

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Tissue Engineering and Regenerative Medicine Aims and scope

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 cartilage-derived 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 β-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.

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Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project funded by the Ministry of Health & Welfare, Republic of Korea (HI17C2191).

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Author notes

  1. Dong Il Shin and Yong Jun Jin contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University Graduate School, 206 Worldcup-ro, Youngtong-gu, Suwon, 16499, Republic of Korea

    Dong Il Shin & Byoung-Hyun Min

  2. Cell Therapy Center, Ajou University School of Medicine, 206 Worldcup-ro, Youngtong-gu, Suwon, 16499, Republic of Korea

    Dong Il Shin, Yong Jun Jin, Sujin Noh, Hee-Woong Yun, Do Young Park & Byoung-Hyun Min

  3. Department of Biomedical Sciences, Ajou University Graduate School, 206 Worldcup-ro, Youngtong-gu, Suwon, 16499, Republic of Korea

    Sujin Noh & Do Young Park

  4. Department of Orthopedic Surgery, Ajou University School of Medicine, 206 Worldcup-ro, Youngtong-gu, Suwon, 16499, Republic of Korea

    Yong Jun Jin, Hee-Woong Yun, Do Young Park & Byoung-Hyun Min

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  1. Dong Il Shin
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Contributions

The experiments were conceptualized and designed by DIS, JYJ, and BHM. The data collection and extraction were performed by DIS, JYJ and SJN. DIS, JYJ, HWY and DYP analyzed the data through productive discussions. DIS, JYJ and DYP were involved in writing and editing. BHM contributed to supervision. All authors read and approved the final manuscript.

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Correspondence to Byoung-Hyun Min.

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The authors declare that they have no conflicts of interest.

Ethical statement

The experiments were conducted with the approval of the Institutional Review Board (IRB) of Ajou University Medical Center (AJIRB-CRO-07–139) and the Institutional Animal Care and Use Committee (IACUC) in Ajou University (IACUC approval No. 2020–0017).

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Shin, D.I., Jin, Y.J., Noh, S. et al. Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p. Tissue Eng Regen Med 21, 487–497 (2024). https://doi.org/10.1007/s13770-023-00618-w

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  • DOI: https://doi.org/10.1007/s13770-023-00618-w

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