Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Neurosci Lett. 2010 Mar 19;472(2):79-84. doi: 10.1016/j.neulet.2010.01.012. Epub 2010 Jan 15.
Chondroitin sulfate proteoglycan (CSPG) is a major component of glial scar to restrict axonal regeneration in the lesion site after spinal cord injury (SCI). Chondroitinase ABC (ChABC), a bacteria enzyme, which has been demonstrated to digest the glycosaminoglycan (GAG) side chain of CSPG to promote axonal re-growth across the injured site. Our previous study suggested that long-term delivery of ChABC (1U/ml, injection volume 0.6 microl for one animal) via intrathecal catheter could decrease the inhibitory effect of limiting axonal re-growth after SCI. The functional behavior has been shown to improve following ChABC treatment. Little axons re-grow across the lesion site of the spinal cord but not enough to support axon innervations to targets. In this article, we show that ChABC administration combining olfactory mucosa progenitor cell (OMPC) transplantation can promote axonal re-growth across the lesion site and enhance the consistency of stepping in spinally transected rats. These OMPCs generated NG2(+) cell lineages after transplanting into the spinal cord parenchyma, and OMPCs were found to spread and migrate toward the lesion region of spinal cord. Moreover, the spatial and temporal characteristics of the step cycle in rats that receive a complete spinal cord transaction following continuous ChABC supply and OMPC transplantation. The gait characteristics of treated rats on a treadmill were consistent and approached that of intact rats. In future, the mechanism of restoring the injured spinal cord will be further investigated.
软骨素硫酸盐蛋白聚糖(CSPG)是神经胶质瘢痕的主要成分,可限制脊髓损伤(SCI)后损伤部位轴突的再生。软骨素酶 ABC(ChABC)是一种细菌酶,已被证明可消化 CSPG 的糖胺聚糖(GAG)侧链,以促进损伤部位轴突的再生长。我们之前的研究表明,通过鞘内导管长期给予 ChABC(1U/ml,每只动物注射体积为 0.6 微升)可降低 SCI 后限制轴突再生的抑制作用。功能行为改善后,脊髓损伤部位有少量轴突再生,但不足以支持轴突支配靶区。在本文中,我们表明,ChABC 给药联合嗅黏膜祖细胞(OMPC)移植可以促进损伤部位的轴突再生,并增强脊髓横断大鼠的步幅一致性。这些 OMPC 在移植到脊髓实质后产生 NG2(+)细胞谱系,并发现 OMPC 向脊髓损伤区域扩散和迁移。此外,接受完全脊髓横断后持续给予 ChABC 和 OMPC 移植的大鼠步周期的时空特征。接受治疗的大鼠在跑步机上的步态特征是一致的,接近完整大鼠。未来,将进一步研究修复损伤脊髓的机制。