Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury.
Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury.
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DOI：
10.1523/jneurosci.3174-09.2010
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发表时间：
2010-02-24
期刊：
影响因子：
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通讯作者：
Whittemore SR
中科院分区：
文献类型：
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作者：
Cao Q;He Q;Wang Y;Cheng X;Howard RM;Zhang Y;DeVries WH;Shields CB;Magnuson DS;Xu XM;Kim DH;Whittemore SR
脱髓鞘是创伤性脊髓损伤（SCI）后功能障碍的重要原因。我们探讨了联合应用神经营养因子和移植成年大鼠脊髓少突胶质前体细胞（OPCs）是否能促进脊髓损伤后髓鞘再生和功能恢复。睫状神经营养因子（CNTF）是促进OPCs体外分化和存活的最有效的神经营养因子。OPCs用表达EGFP或CNTF的逆转录病毒感染，并在损伤后9天移植到挫伤的成人胸脊髓中。移植后7周，移植的OPCs存活并整合到损伤的脊髓中。与EGFP-OPCs相比，移植CNTF-OPCs的存活增加了4倍。移植的OPCs分化为APC+ OLs，CNTF可显著提高移植OPCs中APC+ OLs的比例。免疫荧光和免疫电镜分析显示，移植的OPCs在损伤的脊髓中形成了围绕轴突的中央髓鞘。与所有其他组相比，在接受CNTF-OPC移植物的动物中，在受伤的epiecenter处的腹外侧索（VLF）或外侧索（LF）中的OL-有髓鞘轴突的数量显著增加。重要的是，75%的大鼠接受CNTF-OPC移植物恢复经颅磁运动诱发电位（tcMMEP）和磁内反射（MIER）反应，表明通过VLF或LF脱髓鞘轴突的传导分别部分恢复。更重要的是，在接受CNTF-OPCs移植物的动物中，后肢运动功能的恢复显著增强。因此，与表达CNTF的OPC移植物联合治疗可以增强创伤性SCI后的髓鞘再生并促进功能恢复。
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 EGFP or CNTF and transplanted into the contused adult thoracic spinal cord 9 days post-injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased 4-fold compared to EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluoresent and immuno-electron 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 epiecenter was significantly increased in animals that received CNTF-OPC grafts compared to all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential (tcMMEP) and magnetic inter-englargement reflex (MIER) 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.