Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury

Takeshi Ikegami, Masaya Nakamura, Junichi Yamane, Hiroyuki Katoh, Seiji Okada, Akio Iwanami, Kota Watanabe, Ken Ishii, Fumikazu Kato, Hiroshi Fujita, Toyomi Takahashi, Hirotaka James Okano, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

We previously reported that the transplantation of neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cord in adult rats and monkeys. In some cases, however, most of the transplanted cells adhered to the cavity wall and failed to migrate and integrate into the host spinal cord. In this study we focused on chondroitin sulfate proteoglycan (CSPG), a known constituent of glial scars that is strongly expressed after spinal cord injury (SCI), as a putative inhibitor of NSPC migration in vivo. We hypothesized that the digestion of CSPG by chondroitinase ABC (C-ABC) might promote the migration of transplanted cells and neurite outgrowth after SCI. An in vitro study revealed that the migration of NSPC-derived cells was inhibited by CSPG and that this inhibitory effect was attenuated by C-ABC pre-treatment. Consistently, an in vivo study of C-ABC treatment combined with NSPC transplantation into injured spinal cord revealed that C-ABC pre-treatment promoted the migration of the transplanted cells, whereas CSPG-immunopositive scar tissue around the lesion cavity prevented their migration into the host spinal cord in the absence of C-ABC pre-treatment. Furthermore, this combined treatment significantly induced the outgrowth of a greater number of growth-associated protein-43-positive fibers at the lesion epicentre, compared with NSPC transplantation alone. These findings suggested that the application of C-ABC enhanced the benefits of NSPC transplantation for SCI by reducing the inhibitory effects of the glial scar, indicating that this combined treatment may be a promising strategy for the regeneration of injured spinal cord.

Original languageEnglish
Pages (from-to)3036-3046
Number of pages11
JournalEuropean Journal of Neuroscience
Volume22
Issue number12
DOIs
Publication statusPublished - 2005 Dec 1

Keywords

  • Central nervous system repair
  • Chondroitin sulfate proteoglycan
  • Glial scar
  • Growth-associated protein-43
  • Neural stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

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