Biochemical and functional characterization of skeletal muscle cells differentiated from tonsil-derived mesenchymal stem cells

Yeonzi Choi, Yu Hwa Nam, Soyeon Jeong, Hee Yoon Lee, Se Young Choi, Saeyoung Park, Sung Chul Jung

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction/Aims: Human tonsils are a readily accessible source of stem cells for the potential treatment of skeletal muscle disorders. We reported previously that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into skeletal muscle cells (SKMCs), which renders TMSCs promising candidates for cell therapy for skeletal muscle disorders. However, the functional properties of the myocytes differentiated from mesenchymal stem cells have not been clearly evaluated. In this study we investigated whether myocytes differentiated from TMSCs (skeletal muscle cells derived from tonsil mesenchymal stem cells [TMSC-SKMCs]) exhibit the functional characteristics of SKMCs. Methods: To test the insulin reactivity of TMSC-SKMCs, the expression of glucose transporter 4 (GLUT4) and phosphatidylinositol 3-kinase/Akt was analyzed after the cells were treated for 30 minutes with 100 nmol/L insulin in normal or high-glucose medium. We also examined whether these cells formed a neuromuscular junction (NMJ) when cocultured with motor neurons, and whether they were stimulated by electrical signals using whole-cell patch clamping. Results: Skeletal muscle cells derived from tonsil mesenchymal stem cells expressed SKMC markers, such as MYOD, MYH3, MYH8, TNNI1, and TTN, at high levels, and exhibited a multinucleated cell morphology and a myotube-like shape. The expression of the acetylcholine receptor and GLUT4 was confirmed in TMSC-SKMCs. In addition, these cells exhibited insulin-mediated glucose uptake, NMJ formation, and transient changes in cell membrane action potential, all of which are representative functions of human SKMCs. Discussion: Tonsil-derived mesenchymal stem cells can be functionally differentiated into SKMCs and may have potential for clinical application for the treatment of skeletal muscle disorders.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalMuscle and Nerve
Volume68
Issue number2
DOIs
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 Wiley Periodicals LLC.

Keywords

  • action potential
  • insulin responsiveness
  • neuromuscular junction
  • skeletal muscle cells
  • tonsil-derived mesenchymal stem cells

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