title: IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors.
abstract: Muscle damage has been shown to enhance the contribution of bone marrow-derived cells (BMDCs) to regenerating skeletal muscle. One responsible cell type involved in this process is a hematopoietic stem cell derivative, the myelomonocytic precursor (MMC). However, the molecular components responsible for this injury-related response remain largely unknown. In this paper, we show that delivery of insulin-like growth factor I (IGF-I) to adult skeletal muscle by three different methods-plasmid electroporation, injection of genetically engineered myoblasts, and recombinant protein injection-increases the integration of BMDCs up to fourfold. To investigate the underlying mechanism, we developed an in vitro fusion assay in which co-cultures of MMCs and myotubes were exposed to IGF-I. The number of fusion events was substantially augmented by IGF-I, independent of its effect on cell survival. These results provide novel evidence that a single factor, IGF-I, is sufficient to enhance the fusion of bone marrow derivatives with adult skeletal muscle.
authors.affiliation: Department of Molecular Pharmacology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sacco
authors.forename: Regis
authors.initials: R
authors.lastname: Doyonnas
authors.forename: Mark A
authors.initials: MA
authors.lastname: LaBarge
authors.forename: Mark M
authors.initials: MM
authors.lastname: Hammer
authors.forename: Peggy
authors.initials: P
authors.lastname: Kraft
authors.forename: Helen M
authors.initials: HM
authors.lastname: Blau
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002459:Cell Fusion; D018920:Coculture Techniques; D018274:Electroporation; D018014:Gene Transfer Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000637:transplantation; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I