IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors.
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.
Sacco
Alessandra
A
Department of Molecular Pharmacology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Doyonnas
Regis
R
LaBarge
Mark A
MA
Hammer
Mark M
MM
Kraft
Peggy
P
Blau
Helen M
HM
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
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I