Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector

A. Shiotani, M. Fukumura, M. Maeda, X. Hou, M. Inoue, T. Kanamori, S. Komaba, K. Washizawa, S. Fujikawa, T. Yamamoto, C. Kadono, K. Watabe, H. Fukuda, K. Saito, Y. Sakai, Y. Nagai, J. Kanzaki, M. Hasegawa

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51 Citations (Scopus)

Abstract

We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene transfer into skeletal muscle. Seven days after the intramuscular injection of LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis muscle with/without bupivacaine treatment and the transgene expression persisted up to 1 month after injection. Recombinant hIGF-I was detected as a major protein species in culture supernatants of a neonatal rat myoblast cell line L6 and thus induced the cells to undergo myogenetic differentiation. The introduction of hIGF-I/SeV into the muscle showed a significant increase in regenerating and split myofibers which were indicative of hypertrophy, and also an increase in the total number of myofibers, in comparison to that seen in the LacZ/SeV-treated control muscle. These results demonstrate that SeV achieves high-level transgene expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may therefore have great potential in the treatment of neuromuscular disorders.

Original languageEnglish
Pages (from-to)1043-1050
Number of pages8
JournalGene Therapy
Volume8
Issue number14
DOIs
Publication statusPublished - 2001 Oct 24

Keywords

  • IGF-I
  • Muscle regeneration
  • Sendai virus vector

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Shiotani, A., Fukumura, M., Maeda, M., Hou, X., Inoue, M., Kanamori, T., Komaba, S., Washizawa, K., Fujikawa, S., Yamamoto, T., Kadono, C., Watabe, K., Fukuda, H., Saito, K., Sakai, Y., Nagai, Y., Kanzaki, J., & Hasegawa, M. (2001). Skeletal muscle regeneration after insulin-like growth factor I gene transfer by recombinant Sendai virus vector. Gene Therapy, 8(14), 1043-1050. https://doi.org/10.1038/sj.gt.3301486