PMID- 16367770 OWN - NLM STAT- MEDLINE DCOM- 20060302 LR - 20131121 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 22 IP - 12 DP - 2005 Dec TI - 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. PG - 3036-46 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. FAU - Ikegami, Takeshi AU - Ikegami T AD - Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan. FAU - Nakamura, Masaya AU - Nakamura M FAU - Yamane, Junichi AU - Yamane J FAU - Katoh, Hiroyuki AU - Katoh H FAU - Okada, Seiji AU - Okada S FAU - Iwanami, Akio AU - Iwanami A FAU - Watanabe, Kota AU - Watanabe K FAU - Ishii, Ken AU - Ishii K FAU - Kato, Fumikazu AU - Kato F FAU - Fujita, Hiroshi AU - Fujita H FAU - Takahashi, Toyomi AU - Takahashi T FAU - Okano, Hirotaka James AU - Okano HJ FAU - Toyama, Yoshiaki AU - Toyama Y FAU - Okano, Hideyuki AU - Okano H LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Chondroitin Sulfate Proteoglycans) RN - 0 (GAP-43 Protein) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Intermediate Filament Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nes protein, rat) RN - 0 (Nestin) RN - 0 (Neurofilament Proteins) RN - 0 (Tubulin) RN - EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases) RN - EC 4.2.2.20 (Chondroitin ABC Lyase) SB - IM MH - 2',3'-Cyclic-Nucleotide Phosphodiesterases MH - Analysis of Variance MH - Animals MH - Cell Differentiation/drug effects/physiology MH - Cell Movement/*drug effects MH - Cell Survival/drug effects MH - Chondroitin ABC Lyase/*pharmacology MH - Chondroitin Sulfate Proteoglycans/metabolism/pharmacology MH - Chromatography, High Pressure Liquid/methods MH - Disease Models, Animal MH - Drug Interactions MH - GAP-43 Protein/metabolism MH - Gene Expression Regulation/physiology MH - Glial Fibrillary Acidic Protein MH - Immunohistochemistry/methods MH - Intermediate Filament Proteins/metabolism MH - Nerve Tissue Proteins/metabolism MH - Nestin MH - Neurofilament Proteins MH - Neurons/*drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord Injuries/*surgery MH - Stem Cell Transplantation/*methods MH - Stem Cells/*drug effects/physiology MH - Time Factors MH - Tubulin EDAT- 2005/12/22 09:00 MHDA- 2006/03/03 09:00 CRDT- 2005/12/22 09:00 PHST- 2005/12/22 09:00 [pubmed] PHST- 2006/03/03 09:00 [medline] PHST- 2005/12/22 09:00 [entrez] AID - EJN4492 [pii] AID - 10.1111/j.1460-9568.2005.04492.x [doi] PST - ppublish SO - Eur J Neurosci. 2005 Dec;22(12):3036-46. doi: 10.1111/j.1460-9568.2005.04492.x.