Promoting and accelerating muscle regeneration through cell therapy in a mouse model

Abstract

Objectives: Skeletal muscle injuries and disorders are universal clinical challenges withdirect andindirectmechanisms and notable residual effects, such as prolonged, intense pain and physical disability. Stem cells, an innovative tool for cell therapy for musculoskeletal disorders, specifically promote skeletal muscle regeneration. This study was aimed at investigating the use ofmesenchymal stem cells (MSCs) and their differentiated myocytes as a cell-based therapy to promote regeneration in damaged or diseased skeletal muscle. Methods: Bone marrow mesenchymal stem cells (BMMSCs) were isolated from the bone marrow of adult mice and grown in tissue culture flasks. The BM-MSCs were positive for CD90 and CD105, and negative for CD45 and CD34. These cells were induced with specific differentiation medium in vitro to differentiate into a skeletal muscle cell lineage over 7 days. Skeletal muscle differentiation was characterized according to morphology through hematoxylin and eosin staining, and scanning electron microscopy. Immunostaining for Myf-6, myosin heavy chain (MHC), and desmindspecific factors for skeletal muscle developmentdwas performed to confirm skeletal muscle differentiation. An in vivo study in a muscle injury model was used to evaluate cell therapy based on naı¨ve stem cells and differentiated myocytes. Results: Cultured mouse BM-MSCS were positive for CD90 and CD105, and negative for CD45 and CD34. These cells developed into skeletal muscle with strong skeletal muscle differentiation potential, as confirmed by immunohistochemistry for the markers Myf6, MHC, and desmin. The differentiated myocytes showed better repair enhancement than undifferentiated stem cells after transplantations into a mouse model of skeletal muscle atrophy. Conclusions: Myocytes derived from BM-MSCs may be incorporated into muscular atrophy treatment as a biological strategy for managing skeletal muscle diseases and injuries, thus advancing cell-based clinical treatments.