Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury
Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury
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DOI：
10.1016/j.expneurol.2009.10.024
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发表时间：
2010-01-01
影响因子：
5.3
通讯作者：
Thomaidou, Dimitra
中科院分区：
文献类型：
--
作者：
Lavdas, Alexandros A.;Chen, Jian;Thomaidou, Dimitra
脊髓损伤后的功能恢复仍然是一个重要的目标。在损伤的脊髓中，抑制性分子和缺乏适当的允许因子的组合导致纤维束重新连接和功能的失败。在中枢神经系统损伤的啮齿动物和灵长类动物模型中的实验性移植已经产生了这样的想法，即许旺细胞（SC）是用于自体移植以辅助损伤的髓鞘形成并在中枢神经系统中递送治疗剂的有希望的候选者。在这项研究中，我们使用逆转录病毒转导基因修饰从转基因GFP小鼠的SC，以过度表达细胞粘附分子L1，促进神经突生长和髓鞘形成的蛋白质。将转导表达L1或其嵌合分泌形式L1-Fc的SC混合，并在脊髓压迫损伤后立即将其移植到成年小鼠的病变部位。我们的结果表明，术后3周，但不是此后，与接受对照载体转导的SC或根本没有细胞的动物相比，移植有表达L1/L1-Fc的SC的小鼠表现出更快的运动恢复。形态学分析表明，加速的功能恢复与移植和宿主SC的早期和增强的髓鞘形成相关。此外，与对照组相比，在L1/L1-Fc组中观察到更多的肾上腺素能纤维发芽进入和穿过病变部位。我们的研究结果表明，移植L1过表达的SC增强了损伤后脊髓修复的早期事件，并可与其他再生促进分子一起考虑组合策略。(C)2009 Elsevier Inc. All rights reserved.
Functional recovery after spinal cord lesion remains an important goal. A combination of inhibitory molecules and lack of appropriate permissive factors in the lesioned spinal cord results in failure of fiber tract reconnection and function. Experimental transplantation in rodent and primate models of CNS injuries has led to the idea that Schwann cells (SCs) are promising candidates for autologous transplantation to assist myelination of lesions and to deliver therapeutic agents in the CNS. In this study, we used retroviral transduction to genetically modify SCs from transgenic GFP-mice in order to overexpress the cell adhesion molecule L1, a protein promoting neurite outgrowth and implicated in myelination. SCs transduced to express L1 or its chimeric secreted form L1-Fc were mixed and grafted rostrally to the lesion site of adult mice immediately after spinal cord compression injury. Our results indicate that 3 weeks postoperatively, but not thereafter, mice transplanted with L1/L1-Fc-expressing SCs exhibited faster locomotor recovery as compared to animals which received SCs transduced with a control vector or no cells at all. Morphological analysis indicated that the accelerated functional recovery correlated with earlier and enhanced myelination by both grafted and host SCs. Moreover, increased sprouting of serotonergic fibers into and across the lesion site was observed in the L1/L1-Fc group as compared with controls. Our results suggest that transplantation of L1-overexpressing SCs enhances early events in spinal cord repair after injury and may be considered in combinatorial strategies together with other regeneration-promoting molecules. (C) 2009 Elsevier Inc. All rights reserved.