Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
J Neurosci. 2010 Feb 24;30(8):2989-3001. doi: 10.1523/JNEUROSCI.3174-09.2010.
Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC(+)) OLs, and CNTF significantly increased the percentage of APC(+) OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI.
脱髓鞘是外伤性脊髓损伤 (SCI) 后功能障碍的原因之一。我们探讨了神经营养因子与成年大鼠脊髓少突胶质前体细胞 (OPC) 移植联合应用是否能增强 SCI 后的髓鞘再生和功能恢复。睫状神经营养因子 (CNTF) 是体外促进少突胶质细胞 (OL) 分化和 OPC 存活最有效的神经营养因子。将携带增强型绿色荧光蛋白 (EGFP) 或 CNTF 的逆转录病毒感染 OPC 后，于损伤后 9 天移植到挫伤的成年大鼠胸段脊髓。移植后 7 周，移植的 OPC 存活并整合到损伤的脊髓中。与 EGFP-OPC 相比，移植的 CNTF-OPC 存活增加了 4 倍。移植的 OPC 分化为腺瘤性结肠息肉病 (APC(+)) OL，CNTF 显著增加了移植 OPC 中 APC(+) OL 的比例。免疫荧光和免疫电镜分析显示，移植的 OPC 在损伤脊髓的轴突周围形成了中央髓鞘。与其他各组相比，接受 CNTF-OPC 移植的动物，损伤中心腹外侧束 (VLF) 或外侧束 (LF) 中 OL 髓鞘再生轴突的数量明显增加。重要的是，75%接受 CNTF-OPC 移植的大鼠恢复了经颅磁运动诱发电位和磁间扩大反射反应，表明 VLF 或 LF 中的脱髓鞘轴突的传导分别部分恢复。更重要的是，接受 CNTF-OPC 移植的动物后肢运动功能恢复明显增强。因此，表达 CNTF 的 OPC 移植联合治疗可以增强外伤性 SCI 后的髓鞘再生和功能恢复。
