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, Koota Watanabe, Ken Ishii, Fumikazu Kato, Hiroshi Fujita, Toyomi Takahashi, Hirotaka James Okano, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

128 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

Fingerprint

Chondroitin ABC Lyase
GAP-43 Protein
Neural Stem Cells
Stem Cell Transplantation
Spinal Cord Injuries
Cell Movement
Chondroitin Sulfate Proteoglycans
Stem Cells
Transplants
Spinal Cord Regeneration
Cicatrix
Spinal Cord
Neuroglia
Therapeutics
Haplorhini
Digestion
Transplantation

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

In: European Journal of Neuroscience, Vol. 22, No. 12, 12.2005, p. 3036-3046.

Research output: Contribution to journalArticle

Ikegami, Takeshi ; Nakamura, Masaya ; Yamane, Junichi ; Katoh, Hiroyuki ; Okada, Seiji ; Iwanami, Akio ; Watanabe, Koota ; Ishii, Ken ; Kato, Fumikazu ; Fujita, Hiroshi ; Takahashi, Toyomi ; Okano, Hirotaka James ; Toyama, Yoshiaki ; Okano, Hideyuki. / 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. In: European Journal of Neuroscience. 2005 ; Vol. 22, No. 12. pp. 3036-3046.
@article{ae3e489a19a842b4a1ed03b0b55f810b,
title = "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",
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.",
keywords = "Central nervous system repair, Chondroitin sulfate proteoglycan, Glial scar, Growth-associated protein-43, Neural stem cell",
author = "Takeshi Ikegami and Masaya Nakamura and Junichi Yamane and Hiroyuki Katoh and Seiji Okada and Akio Iwanami and Koota Watanabe and Ken Ishii and Fumikazu Kato and Hiroshi Fujita and Toyomi Takahashi and Okano, {Hirotaka James} and Yoshiaki Toyama and Hideyuki Okano",
year = "2005",
month = "12",
doi = "10.1111/j.1460-9568.2005.04492.x",
language = "English",
volume = "22",
pages = "3036--3046",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - 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

AU - Ikegami, Takeshi

AU - Nakamura, Masaya

AU - Yamane, Junichi

AU - Katoh, Hiroyuki

AU - Okada, Seiji

AU - Iwanami, Akio

AU - Watanabe, Koota

AU - Ishii, Ken

AU - Kato, Fumikazu

AU - Fujita, Hiroshi

AU - Takahashi, Toyomi

AU - Okano, Hirotaka James

AU - Toyama, Yoshiaki

AU - Okano, Hideyuki

PY - 2005/12

Y1 - 2005/12

N2 - 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.

AB - 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.

KW - Central nervous system repair

KW - Chondroitin sulfate proteoglycan

KW - Glial scar

KW - Growth-associated protein-43

KW - Neural stem cell

UR - http://www.scopus.com/inward/record.url?scp=29344451629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29344451629&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.2005.04492.x

DO - 10.1111/j.1460-9568.2005.04492.x

M3 - Article

VL - 22

SP - 3036

EP - 3046

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 12

ER -