G.O.6 Sjl dystrophic mice express large amount of human muscle proteins following systemic delivery of human adipose-derived stem cells

Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or defective muscular proteins. The murine model for limb-girdle muscular dystrophy 2B (LGMD2B), the sjl mice, carry a deletion in the dysferlin gene that causes a reduction in the protein levels to 15% of normal. The mice show muscle weakness that begins at 4–6 weeks and is nearly complete by 8 months of age. The possibility to restore the defective muscle protein and improve muscular performance by cell therapy is a promising approach for the treatment of LGMD or other forms of progressive muscular dystrophies (PMD). Here we have injected human adipose stem cells (hASCs) in the sjl mice, without immunosuppression, aiming to assess their ability to: engraft into recipient dystrophic muscle after systemic delivery; form chimeric human/mouse muscle fibers; express human muscle proteins in the dystrophic host and improve muscular performance. We show for the first time that hASCs are not rejected after systemic injection even without immunosuppression, are able to fuse with the host muscle, express a significant amount of human muscle proteins and improve motor ability of injected animals. These results may have important applications for future therapy in patients with different forms of muscular dystrophies.