title: Adipose tissue-derived stem cell secreted IGF-1 protects myoblasts from the negative effect of myostatin.
abstract: Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.
authors.affiliation: Applied Stem Cell Research Center, University Medical Center Regensburg, 93053 Regensburg, Germany ; Department of Trauma Surgery, Center of Plastic and Hand Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gehmert
authors.affiliation: Applied Stem Cell Research Center, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Carina
authors.identifier: 0000-0001-7271-2101
authors.initials: C
authors.lastname: Wenzel
authors.affiliation: Applied Stem Cell Research Center, University Medical Center Regensburg, 93053 Regensburg, Germany ; Department of Trauma Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Markus
authors.identifier: 0000-0001-7631-0476
authors.initials: M
authors.lastname: Loibl
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Gero
authors.identifier: 0000-0001-8398-8349
authors.initials: G
authors.lastname: Brockhoff
authors.affiliation: Department of Trauma Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Michaela
authors.identifier: 0000-0001-7478-5697
authors.initials: M
authors.lastname: Huber
authors.affiliation: Department of Trauma Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Werner
authors.identifier: 0000-0002-3099-1402
authors.initials: W
authors.lastname: Krutsch
authors.affiliation: Department of Trauma Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nerlich
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gosau
authors.affiliation: Department of Trauma Surgery, Center of Plastic and Hand Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Silvan
authors.initials: S
authors.lastname: Klein
authors.affiliation: Department of Dermatology, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schreml
authors.affiliation: Department of Trauma Surgery, Center of Plastic and Hand Surgery, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Prantl
authors.affiliation: Applied Stem Cell Research Center, University Medical Center Regensburg, 93053 Regensburg, Germany ; Department of Obstetrics and Gynecology, University Medical Center Regensburg, 93053 Regensburg, Germany.
authors.forename: Sanga
authors.identifier: 0000-0002-8457-4591
authors.initials: S
authors.lastname: Gehmert
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002459:Cell Fusion; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects*; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D055435:Myostatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D017570:MyoD Protein; D055435:Myostatin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I