title: Bone marrow transplantation in dysferlin-deficient mice results in a mild functional improvement.
abstract: Dysferlinopathies are caused by mutations in the DYSF gene. Dysferlin is a protein mainly expressed in the skeletal muscle and monocytes. Cell therapy constitutes a promising tool for the treatment of muscular dystrophies. The aim of our study was to evaluate the effect of bone marrow transplantation (BMT) using the A/J Dysf(prmd) mouse model of dysferlinopathy. For that purpose, we studied dysferlin expression by western blot and/or immunohistochemistry in transplanted mice and controls. Computerized analyses of locomotion and electrophysiological techniques were also performed to test the functional improvement. We observed dysferlin expression in splenocytes, but not in the skeletal muscle of the transplanted mice. However, the locomotion test, electromyography studies, and muscle histology showed an improvement in all transplanted mice that was more significant in the animals transplanted with dysferlin⁺/⁺ cells. In conclusion, although BMT restores dysferlin expression in monocytes, but not in skeletal muscle, muscle function was partially recovered. We propose that the slight improvement observed in the functional studies could be related with factors, such as the hepatocyte growth factor, released after BMT that prevented muscle degeneration.
authors.affiliation: 1 Laboratori de Malalties Neuromusculars, Institut de Recerca de HSCSP, Universitat Autònoma de Barcelona (UAB) , Barcelona, Spain .
authors.forename: Bàrbara
authors.initials: B
authors.lastname: Flix
authors.forename: Xavier
authors.initials: X
authors.lastname: Suárez-Calvet
authors.forename: Jordi
authors.initials: J
authors.lastname: Díaz-Manera
authors.forename: Eva
authors.initials: E
authors.lastname: Santos-Nogueira
authors.forename: Renzo
authors.initials: R
authors.lastname: Mancuso
authors.forename: Jordi
authors.initials: J
authors.lastname: Barquinero
authors.forename: Miquel
authors.initials: M
authors.lastname: Navas
authors.forename: Xavier
authors.initials: X
authors.lastname: Navarro
authors.forename: Isabel
authors.initials: I
authors.lastname: Illa
authors.forename: Eduard
authors.initials: E
authors.lastname: Gallardo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D000073939:Dysferlin; D004576:Electromyography; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins; D017228:Hepatocyte Growth Factor