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

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.

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.

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.

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.