title: Partial dysferlin reconstitution by adult murine mesoangioblasts is sufficient for full functional recovery in a murine model of dysferlinopathy.
abstract: Dysferlin deficiency leads to a peculiar form of muscular dystrophy due to a defect in sarcolemma repair and currently lacks a therapy. We developed a cell therapy protocol with wild-type adult murine mesoangioblasts. These cells differentiate with high efficiency into skeletal muscle in vitro but differ from satellite cells because they do not express Pax7. After intramuscular or intra-arterial administration to SCID/BlAJ mice, a novel model of dysferlinopathy, wild-type mesoangioblasts efficiently colonized dystrophic muscles and partially restored dysferlin expression. Nevertheless, functional assays performed on isolated single fibers from transplanted muscles showed a normal repairing ability of the membrane after laser-induced lesions; this result, which reflects gene correction of an enzymatic rather than a structural deficit, suggests that this myopathy may be easier to treat with cell or gene therapy than other forms of muscular dystrophies.
authors.affiliation: Division of Regenerative Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Manera
authors.forename: T
authors.initials: T
authors.lastname: Touvier
authors.forename: A
authors.initials: A
authors.lastname: Dellavalle
authors.forename: R
authors.initials: R
authors.lastname: Tonlorenzi
authors.forename: F S
authors.initials: FS
authors.lastname: Tedesco
authors.forename: G
authors.initials: G
authors.lastname: Messina
authors.forename: M
authors.initials: M
authors.lastname: Meregalli
authors.forename: C
authors.initials: C
authors.lastname: Navarro
authors.forename: L
authors.initials: L
authors.lastname: Perani
authors.forename: C
authors.initials: C
authors.lastname: Bonfanti
authors.forename: I
authors.initials: I
authors.lastname: Illa
authors.forename: Y
authors.initials: Y
authors.lastname: Torrente
authors.forename: G
authors.initials: G
authors.lastname: Cossu
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001681:Biological Assay; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology* / Q000637:transplantation; D004195:Disease Models, Animal; D000073939:Dysferlin; D007249:Inflammation / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020127:Recovery of Function / Q000502:physiology*
chemical_list: C497505:Dysf protein, mouse; D000073939:Dysferlin; D008565:Membrane Proteins