Genetically Engineered Mesenchymal Stem Cells With Human Micro-dystrophin Improve Skeletal Muscle Histopathology in Mdx Mice

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive inherited muscular disease with no effective treatment to date. In the present study, we combined gene repair and cell therapy to develop genetically-modified mdx mesenchymal stem cells with micro-dystrophin (microdys-mMSCs) and explore their feasibility as a treatment for DMD. After generation and characterizing of the microdys-mMSCs, these cells were transplanted into the mdx mouse model. The dystrophic tissue gradually alleviated over time both in gastrocnemius and diaphragmatic mouse muscles. The percentage of centrally nucleated myofibers (CNFs), fiber cross-sectional area (CSA), and connective tissue area also significantly decreased in these muscles. Furthermore, dystrophin protein expression was partially restored and creatine phosphokinase (CK) levels were significantly reduced in the mice. These findings indicate that combined use of gene repair and cell therapy has promise for the treatment of muscular disease in humans.