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
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
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DOI：
10.1111/j.1460-9568.2005.04492.x
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Okano, H
中科院分区：
文献类型：
--
作者：
Ikegami, T;Nakamura, M;Okano, H
我们以前报道过神经干/祖细胞（NSPCs）移植可以促进成年大鼠和猴脊髓损伤的修复。然而，在某些情况下，大多数移植的细胞粘附在腔壁上，未能迁移和整合到宿主脊髓中。在这项研究中，我们专注于硫酸软骨素蛋白聚糖（CSPG），一个已知的组成部分的胶质瘢痕，强烈表达脊髓损伤（SCI）后，作为一个假定的抑制剂NSPC迁移在体内。我们推测CSPG被软骨素酶ABC（C-ABC）消化可能促进SCI后移植细胞的迁移和神经突起的生长。体外研究表明，NSPC衍生的细胞的迁移被CSPG抑制，并且这种抑制作用被C-ABC预处理减弱。同样，C-ABC治疗结合NSPC移植到损伤脊髓中的体内研究显示，C-ABC预处理促进了移植细胞的迁移，而在没有C-ABC预处理的情况下，损伤腔周围的CSPG免疫阳性瘢痕组织阻止了它们迁移到宿主脊髓中。此外，与单独NSPC移植相比，这种联合治疗显著诱导了更多数量的生长相关蛋白-43阳性纤维在病变中心的生长。这些结果表明，应用C-ABC通过减少胶质瘢痕的抑制作用增强了NSPC移植治疗SCI的益处，表明这种联合治疗可能是损伤脊髓再生的一种有前途的策略。
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.