title: Systemic delivery of allogenic muscle stem cells induces long-term muscle repair and clinical efficacy in duchenne muscular dystrophy dogs.
abstract: Duchenne muscular dystrophy (DMD) is a genetic progressive muscle disease resulting from the lack of dystrophin and without effective treatment. Adult stem cell populations have given new impetus to cell-based therapy of neuromuscular diseases. One of them, muscle-derived stem cells, isolated based on delayed adhesion properties, contributes to injured muscle repair. However, these data were collected in dystrophic mice that exhibit a relatively mild tissue phenotype and clinical features of DMD patients. Here, we characterized canine delayed adherent stem cells and investigated the efficacy of their systemic delivery in the clinically relevant DMD animal model to assess potential therapeutic application in humans. Delayed adherent stem cells, named MuStem cells (muscle stem cells), were isolated from healthy dog muscle using a preplating technique. In vitro, MuStem cells displayed a large expansion capacity, an ability to proliferate in suspension, and a multilineage differentiation potential. Phenotypically, they corresponded to early myogenic progenitors and uncommitted cells. When injected in immunosuppressed dystrophic dogs, they contributed to myofiber regeneration, satellite cell replenishment, and dystrophin expression. Importantly, their systemic delivery resulted in long-term dystrophin expression, muscle damage course limitation with an increased regeneration activity and an interstitial expansion restriction, and persisting stabilization of the dog's clinical status. These results demonstrate that MuStem cells could provide an attractive therapeutic avenue for DMD patients.
authors.affiliation: INRA, UMR 703 Développement et Pathologie du Tissu Musculaire, Nantes, France. karl.rouger@nantes.inra.fr
authors.forename: Karl
authors.initials: K
authors.lastname: Rouger
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.forename: Laurence
authors.initials: L
authors.lastname: Dubreil
authors.forename: Jack-Yves
authors.initials: JY
authors.lastname: Deschamps
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Guiner
authors.forename: Gregory
authors.initials: G
authors.lastname: Jouvion
authors.forename: Bruno
authors.initials: B
authors.lastname: Delorme
authors.forename: Blandine
authors.initials: B
authors.lastname: Lieubeau
authors.forename: Marine
authors.initials: M
authors.lastname: Carlus
authors.forename: Benoît
authors.initials: B
authors.lastname: Fornasari
authors.forename: Marine
authors.initials: M
authors.lastname: Theret
authors.forename: Priscilla
authors.initials: P
authors.lastname: Orlando
authors.forename: Mireille
authors.initials: M
authors.lastname: Ledevin
authors.forename: Céline
authors.initials: C
authors.lastname: Zuber
authors.forename: Isabelle
authors.initials: I
authors.lastname: Leroux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Deleau
authors.forename: Lydie
authors.initials: L
authors.lastname: Guigand
authors.forename: Isabelle
authors.initials: I
authors.lastname: Testault
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Le Rumeur
authors.forename: Marc
authors.initials: M
authors.lastname: Fiszman
authors.forename: Yan
authors.initials: Y
authors.lastname: Chérel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004285:Dogs; D016189:Dystrophin / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007273:Injections, Intramuscular; D032342:Muscle Cells / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology; D014184:Transplantation, Homologous
chemical_list: D016189:Dystrophin; D007166:Immunosuppressive Agents