Agudo M, Woodhoo A, Webber D, Mirsky R, Jessen K R, McMahon S B
The Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, United Kingdom.
Glia. 2008 Sep;56(12):1263-70. doi: 10.1002/glia.20695.
There is a strong current interest in the use of cell transplantation for the treatment of spinal cord injuries. We report here the novel and potentially useful properties of an early cell in the Schwann cell lineage, the Schwann cell precursor (SCP). The experiments reveal a striking difference between these cells and Schwann cells when transplanted into the CNS. Unlike Schwann cells, SCPs thrive in the CNS where they initially proliferate rapidly but then fall out of division, thus effectively filling up the large cystic cavities formed following crush injury, while avoiding tumor formation. By 8 weeks, SCPs had started to express S100beta protein, a marker that differentiates Schwann cells from SCPs and had formed an apparently stable, vascularized cell mass, which created a continuous cellular bridge across the cystic cavities. The formation of the surrounding glial scar was reduced by local spread of the transplanted cells into the surrounding CNS tissue, where the cells integrated intimately with astrocytes and attenuated the physical barrier they normally form. SCP transplantation also altered and reduced the expression of chondroitin sulfate proteoglycans around the injury site. Caudal to the SCP transplants there was a large increase in the number of axons, compared with that seen in nontransplanted control tissue, showing that the implants effectively support axonal growth or sprouting. SCPs have advantageous attributes for CNS repair, despite the fact that sticky tape removal and ladder crossing tests at 8 weeks did not reveal significant functional improvements when compared with control animals.
目前,细胞移植治疗脊髓损伤备受关注。我们在此报告雪旺细胞谱系中的一种早期细胞——雪旺细胞前体(SCP)的新特性及其潜在用途。实验揭示了这些细胞与雪旺细胞移植到中枢神经系统(CNS)时的显著差异。与雪旺细胞不同,SCPs在中枢神经系统中能够茁壮成长,它们最初迅速增殖,但随后停止分裂,从而有效地填充了挤压伤后形成的大囊腔,同时避免肿瘤形成。到8周时,SCPs开始表达S100β蛋白,这是一种区分雪旺细胞和SCPs的标志物,并形成了一个明显稳定的、血管化的细胞团,在囊腔之间形成了连续的细胞桥。移植细胞向周围中枢神经系统组织局部扩散,减少了周围胶质瘢痕的形成,在该组织中,细胞与星形胶质细胞紧密整合,削弱了它们通常形成的物理屏障。SCP移植还改变并减少了损伤部位周围硫酸软骨素蛋白聚糖的表达。与未移植的对照组织相比,SCP移植部位尾侧的轴突数量大幅增加,表明植入物有效地支持了轴突生长或发芽。尽管在8周时进行的粘胶带去除和爬梯试验显示,与对照动物相比,功能没有显著改善,但SCPs对中枢神经系统修复具有有利特性。