title: Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.
abstract: Muscle satellite cells (SCs) are stem cells that reside in skeletal muscles and contribute to regeneration upon muscle injury. SCs arise from skeletal muscle progenitors expressing transcription factors Pax3 and/or Pax7 during embryogenesis in mice. However, it is unclear whether these fetal progenitors possess regenerative ability when transplanted in adult muscle. Here we address this question by investigating whether fetal skeletal muscle progenitors (FMPs) isolated from Pax3(GFP/+) embryos have the capacity to regenerate muscle after engraftment into Dystrophin-deficient mice, a model of Duchenne muscular dystrophy. The capacity of FMPs to engraft and enter the myogenic program in regenerating muscle was compared with that of SCs derived from adult Pax3(GFP/+) mice. Transplanted FMPs contributed to the reconstitution of damaged myofibers in Dystrophin-deficient mice. However, despite FMPs and SCs having similar myogenic ability in culture, the regenerative ability of FMPs was less than that of SCs in vivo. FMPs that had activated MyoD engrafted more efficiently to regenerate myofibers than MyoD-negative FMPs. Transcriptome and surface marker analyses of these cells suggest the importance of myogenic priming for the efficient myogenic engraftment. Our findings suggest the regenerative capability of FMPs in the context of muscle repair and cell therapy for degenerative muscle disease.
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakai
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sato
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Didier
authors.initials: D
authors.lastname: Montarras
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology* / Q000196:embryology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology / Q000601:surgery; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009210:Myofibrils / Q000235:genetics / Q000502:physiology; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000637:transplantation; D033581:Stem Cell Transplantation / Q000379:methods*; D059467:Transcriptome
chemical_list: D016189:Dystrophin; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse; D049452:Green Fluorescent Proteins