Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury
Intraspinal cord graft of autologous activated Schwann cells efficiently promotes axonal regeneration and functional recovery after rat's spinal cord injury
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DOI：
10.1016/j.brainres.2008.11.098
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发表时间：
2009-02-23
期刊：
影响因子：
2.9
通讯作者：
Guo, Shi-Fu
中科院分区：
文献类型：
--
作者：
Ban, De-Xiang;Kong, Xiao-Hong;Guo, Shi-Fu
近年来，脊髓损伤（SCI）的基础研究取得了长足的进步，在促进有效轴突再生和发芽方面也有了一些新的见解和策略。然而，相对安全和有效的移植技术仍然没有确定。因此，本研究的目的是解决如何移植雪旺细胞以达到最佳治疗效果的问题。为了澄清这个问题，在T10时对大鼠进行脊髓损伤。通过结扎隐神经获得自体激活的雪旺细胞（AASCs），体外分离纯化后，经3种不同途径（I组：静脉内，II组：鞘内，III组：脊髓内）移植到脊髓损伤大鼠体内。采用Basso、Beattie、Bresnahan运动评定量表和足迹分析法对神经功能进行连续评价。我们还评估了移植后2周移植细胞的迁移。应用生物素葡聚糖胺（BDA）顺行追踪技术，我们证实了III组损伤腔周围皮质脊髓束（CST）再生轴突多于其他两组，并通过定量分析进一步证实了这一点。通过免疫组织化学染色，第III组脊髓损伤周围的微环境得到了最大程度的改善。电镜下，Ⅱ、Ⅲ组较Ⅰ组髓鞘较完整，轴突内神经丝较多。结果表明，脊髓内注射AASCs能更有效地促进损伤大鼠后肢运动功能的恢复。此外，完整的髓鞘和轴突中足够的神经丝不足以在SCI后完全恢复功能，这表明重建正常的突触连接是必不可少的。本研究的结果强烈提示，AASCs直接移植到脊髓内可能是有希望的候选人之一，AASCs的移植策略可能有望治疗SCI患者。(C)2008 Elsevier B.V.保留所有权利。
Basic research in spinal cord injury (SCI) has made great strides in recent years, and some new insights and strategies have been applied in promoting effective axonal regrowth and sprouting. However, a relatively safe and efficient transplantation technique remains undetermined. This study, therefore, was aimed to address a question of how to graft Schwann cells to achieve the best possible therapeutic effects. To clarify the issue, the rats were subjected to spinal cord injury at T10. Autologous activated Schwann cells (AASCs) were obtained by prior ligation of saphenous nerve and subsequently isolated and purified in vitro and then grafted into spinal cord-injured rats via three different routes (group I: intravenous, group II: intrathecal and group III: intraspinal cord). Neurologic function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. We also evaluated the migration of the transplanted cells at 2 weeks after transplantation. Using biotinylated dextran amine (BDA) anterograde tracing, we demonstrated that more regenerative axons of corticospinal tract (CST) surrounding the injured cavity in group III than those in the other two groups, and we also confirmed it further by quantitative analysis. The microenvironment surrounding the injured spinal cord has been improved to the greatest extent in group III, as determined by immunohistological staining. Relatively complete myelin sheaths and more neurofilaments in axons were found in groups II and III than those in group I under electron microscopy. The results showed that intraspinal cord injection of AASCs promoted recovery of hindlimb locomotor function of injured rats more efficiently than the other grafting routes. In addition, intact myelin sheaths and sufficient neurofilaments in axons were not adequate for full functional recovery after SCI, suggesting that reestablishment of normal synaptic connection is indispensable. The findings in this study strongly suggest that transplantation of AASCs directly into the spinal cord may be one of the promising candidates for potential scaffold for injured spinal cord, and such strategy of transplantation of AASCs could be hopeful to treat patients with SCI. (C) 2008 Elsevier B.V. All rights reserved.