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Transplantation of Differentiated Tonsil-Derived Mesenchymal Stem Cells Ameliorates Murine Duchenne Muscular Dystrophy via Autophagy Activation

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

BACKGROUND:

Skeletal muscles play many important roles in the human body and any malfunction or disorder of the skeletal muscles can lead to a reduced quality of life. Some skeletal dysfunctions are acquired, such as sarcopenia but others are congenital. Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophy and is caused by a deficiency of the protein, Dystrophin. Currently, there is no clear treatment for DMD, there are only methods that can alleviate the symptoms of the disease. Mesenchymal stem cells, including tonsil-derived mesenchymal stem cells (TMSCs) have been shown to differentiate into skeletal muscle cells (TMSC-myocyte) and can be one of the resources for the treatment of DMD. Skeletal muscle cell characteristics of TMSC-myocytes have been confirmed through changes in morphology and expression of skeletal muscle markers such as Myogenin, Myf6, and MYH families after differentiation.

MEOTHDS:

Based on these characteristics, TMSC-myocytes have been transplanted into mdx mice, a mouse model of DMD, to investigate whether they can help improve the symptoms of DMD. The red fluorescent protein gene was transduced into TMSC (TMSC-R) for tracking transplanted cells.

RESULTS:

Prior to transplantation (TP), it was confirmed whether TMSC-R-myocytes had the same differentiation potential as TMSC-myocytes. Increased expression of dystrophin and autophagy markers in the TP group compared with the sham group was confirmed in the gastrocnemius muscle 12 weeks after TP.

CONCLUSION:

These results demonstrate muscle regeneration and functional recovery of mdx via autophagy activation following TMSC-myocyte TP.

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Acknowledgements

This study was supported by a grant from the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science & ICT (grant number, 2017M3A9B3063636), the Basic Science Research Pro-gram through the NRF funded by the Ministry of Education (2019R1I1A1A01060308) and the RP-Grant 2021 of Ewha Womans University.

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  1. Saeyoung Park and Soyeon Jeong have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, 07804, Republic of Korea

    Saeyoung Park, Soyeon Jeong, Yu Hwa Nam, Yoonji Yum & Sung-Chul Jung

  2. Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, 07804, Republic of Korea

    Yu Hwa Nam & Sung-Chul Jung

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  1. Saeyoung Park
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Correspondence to Sung-Chul Jung.

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The study protocol was approved by the Ewha Womans University Medical Center (EWUMC) institutional review board (IRB number: ECT-2011–09-003). All the experimental procedures were reviewed and approved by the ethics committee for animal research at Ewha Woman’s University (EUM20-051). Informed Consent Statement: Informed written consent was obtained from all the patients participating in the study.

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Park, S., Jeong, S., Nam, Y.H. et al. Transplantation of Differentiated Tonsil-Derived Mesenchymal Stem Cells Ameliorates Murine Duchenne Muscular Dystrophy via Autophagy Activation. Tissue Eng Regen Med 19, 1283–1294 (2022). https://doi.org/10.1007/s13770-022-00489-7

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  • DOI: https://doi.org/10.1007/s13770-022-00489-7

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