Research Professor Ewha Womans University Seoul, Republic of Korea
Abstract: Volumetric muscle wasting (VML) is a traumatic injury characterized by irreversible removal of skeletal muscle, resulting in loss of tissue function and lifelong disability. However, treatments for VML are limited to scar tissue removal and autologous muscle transplantation. Skeletal muscle can regenerate after injury, but in VML, when tissue loss is severe, the natural regenerative capacity of muscle tissue is impaired. In this study, we evaluated the potential of spheroids derived from mesenchymal stem cells (MSCs) to treat VML, where muscle regeneration is poor. In previous studies, we have confirmed that tonsil-derived mesenchymal stem cells (TMSCs) can be differentiated into skeletal muscle cells (SKMCs), and these cells have characteristics of skeletal muscles. Spheroids were formed using TMSC-derived skeletal muscle cells (TMSC-SKMC-spheroids) in microwell. To evaluate the treatment effects, grip test, gait analysis and nerve conduction study were performed after treated the mixture with TMSC-SKMC-spheroids and medical collagen into a VML rat model. The VLM model treated with TMSC-SKMC-spheroids showed improved motor function of the hindlimb and regeneration of the gastrocnemius muscle. These regeneration of the muscle after treatment was confirmed by changes in the expression of myokine markers. Taken together, these results indicate the therapeutic potential of TMSC-SKMC-spheroids mixed with collagen for VML. Furthermore, TMSC-SKMC-spheroids are expected to be developed as one of the promising therapeutic resources for hereditary, degenerative muscle diseases.
Funding Source: This study was supported by a Basic Science Research Program through the NRF funded by the Ministry of Education (2022R1I1A01064295) and KFRM funded by Ministry of Science and ICT, and Ministry of Health and Welfare (23A0201L1).