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Published 7 November 2005. doi:10.1083/jcb.200506123
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 171, Number 3, 483-492
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Article

IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors



Alessandra Sacco1, Regis Doyonnas1, Mark A. LaBarge2, Mark M. Hammer1,2, Peggy Kraft1,2, and Helen M. Blau1,2

1 Department of Molecular Pharmacology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305
2 Department of Microbiology and Immunology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305

Correspondence to Helen M. Blau: hblau{at}stanford.edu

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.

M.A. LaBarge's present address is Lawrence Berkeley National Laboratory, Berkeley, CA 94720.

Abbreviations used in this paper: ß-gal, ß-galactosidase; BMDC, bone marrow–derived cell; BMT, bone marrow transplant; DM, differentiation medium; GM, growth medium; HSC, hematopoietic stem cell; IGF-I, insulin-like growth factor I; MGF, mechano growth factor; MMC, myelomonocytic precursor; TA, tibialis anterior.


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