Human Mesenchymal Stem Cell-Derived Skeletal Muscle Cell Spheroids for Treating Dexamethasone-Induced Sarcopenia

Abstract

Background:Sarcopenia, a musculoskeletal disease associated with aging or certain factors, is characterized by a reduction in muscle mass, strength, and performance. Dexamethasone (DEX)-induced muscular atrophy in animals, which shows a significant decrease in muscle mass, strength, and function, serves as a model for sarcopenia. Mesenchymal stem cell-based therapies, particularly those using 3D cultured spheroids, have emerged as a prominent area in muscle regeneration. Previous research has demonstrated that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into skeletal muscle cells (SKMCs) that exhibit attributes of skeletal muscles.Methods:Spheroids formed from TMSC-derived skeletal muscle cells (TMSC-SKMC-spheroids) were produced using microwells and subsequently transplanted into a sarcopenia model. This model utilized a dexamethasone (DEX)-induced muscular atrophy rat to mimic sarcopenia. The effectiveness of TMSC-SKMC-spheroid transplantation was assessed through grip strength tests, running fatigue tests, measurements of gastrocnemius muscle thickness and weight, and histopathological evaluations.Results:Post-transplantation, the rat models exhibited improvement in hind limb motor functions and gastrocnemius muscle regeneration. Additionally, the neuromuscular junctions in the gastrocnemius muscle of the transplantation group were restored.Conclusion:These findings demonstrate the therapeutic potential of TMSC-SKMC-spheroids in the DEX-induced atrophy rat model and suggest their promise as a valuable therapeutic resource for sarcopenia caused by various factors.