title: Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles.
abstract: Satellite cells reside beneath the basal lamina of skeletal muscle fibers and include cells that act as precursors for muscle growth and repair. Although they share a common anatomical localization and typically are considered a homogeneous population, satellite cells actually exhibit substantial heterogeneity. We used cell-surface marker expression to purify from the satellite cell pool a distinct population of skeletal muscle precursors (SMPs) that function as muscle stem cells. When engrafted into muscle of dystrophin-deficient mdx mice, purified SMPs contributed to up to 94% of myofibers, restoring dystrophin expression and significantly improving muscle histology and contractile function. Transplanted SMPs also entered the satellite cell compartment, renewing the endogenous stem cell pool and participating in subsequent rounds of injury repair. Together, these studies indicate the presence in adult skeletal muscle of prospectively isolatable muscle-forming stem cells and directly demonstrate the efficacy of myogenic stem cell transplant for treating muscle degenerative disease.
authors.affiliation: Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02115, USA.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cerletti
authors.forename: Sara
authors.initials: S
authors.lastname: Jurga
authors.forename: Carol A
authors.initials: CA
authors.lastname: Witczak
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shadrach
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
mesh_terms: D053687:Adult Stem Cells / Q000737:chemistry / Q000166:cytology*; D000818:Animals; D002469:Cell Separation; D016189:Dystrophin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000628:therapy; D032496:Satellite Cells, Skeletal Muscle / Q000737:chemistry / Q000166:cytology*; D033581:Stem Cell Transplantation
chemical_list: D016189:Dystrophin; D008565:Membrane Proteins