title: SJL dystrophic mice express a significant amount of human muscle proteins following systemic delivery of human adipose-derived stromal cells without immunosuppression.
abstract: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence of or defective muscular proteins. The murine model for limb-girdle muscular dystrophy 2B (LGMD2B), the SJL mice, carries 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 of restoring the defective muscle protein and improving muscular performance by cell therapy is a promising approach for the treatment of LGMDs or other forms of progressive muscular dystrophies. Here we have injected human adipose stromal cells (hASCs) into 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.
authors.affiliation: Human Genome Research Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
authors.forename: Natássia M
authors.initials: NM
authors.lastname: Vieira
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Bueno
authors.forename: Vanessa
authors.initials: V
authors.lastname: Brandalise
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Moraes
authors.forename: Eder
authors.initials: E
authors.lastname: Zucconi
authors.forename: Mariane
authors.initials: M
authors.lastname: Secco
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Suzuki
authors.forename: Maristela M
authors.initials: MM
authors.lastname: Camargo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bartolini
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002478:Cells, Cultured; D000073939:Dysferlin; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation
chemical_list: C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins