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IGF-I gene transfer by electroporation promotes regeneration in a muscle injury model

Gene Therapy volume 10, pages 612–620 (2003)Cite this article

Abstract

The goal of this study was to determine whether insulin-like growth factor-I (IGF-I) gene delivery by electroporation promotes repair after muscle injury. An injury–repair model was created using mice in which a hamstring muscle was cut and sutured. A total of 50 μg of IGF-I DNA or green fluorescent protein (GFP) DNA (both in pCAGGS) was injected into the lesion and introduced into muscle cells by electrostimulation using an electric pulse generator. The number of regenerating muscle fibers in the IGF-I DNA group was significantly more than that in the GFP DNA group at 2 weeks after injection. The diameter of regenerating muscle fibers from the IGF-I DNA group was larger than that of the GFP DNA group at 4 weeks after injection. There was no significant difference in the serum IGF-I concentration between the IGF-I DNA group and the GFP DNA group at 1, 2, and 4 weeks after injection. However, muscle IGF-I concentration in the IGF-I DNA injection group was significantly greater than that in the GFP DNA injection group at 2 weeks after injection. These results demonstrated that the effects of enhanced IGF-I production were local and limited to the injected area. The ratio (injected/uninjected; intact) of the amplitude of compound muscle action potentials (CMAP) in the IGF-I DNA injection group was greater than that in the GFP DNA injection group at 4 weeks after injection and of the control group. In conclusion, IGF-I gene transfer by electroporation proved to be a simple, safe, inexpensive, and effective method to promote the regeneration of injured muscles in our injury model.

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Acknowledgements

We thank Dr Peter S Rotwein for providing us with rat IGF-I cDNA, and Dr Shiraishi and Ms Miyazaki for their technical assistance.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Kochi Medical School, Nankoku, Kochi, Japan

    T Takahashi, K Ishida, K Itoh & H Yamamoto

  2. Medical Research Center, Kochi Medical School, Nankoku, Kochi, Japan

    Y Konishi, K-I Yagyu & A Tominaga

  3. Department of Medical Biology, Kochi Medical School, Nankoku, Kochi, Japan

    A Tominaga

  4. Department of Molecular Therapy, Division of Stem Cell Regulation Research, Osaka University Medical School, Suita, Osaka, Japan

    J-I Miyazaki

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  1. T Takahashi
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  2. K Ishida
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  3. K Itoh
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  4. Y Konishi
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  5. K-I Yagyu
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  7. J-I Miyazaki
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  8. H Yamamoto
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Takahashi, T., Ishida, K., Itoh, K. et al. IGF-I gene transfer by electroporation promotes regeneration in a muscle injury model. Gene Ther 10, 612–620 (2003). https://doi.org/10.1038/sj.gt.3301900

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