Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
Exp Neurol. 2010 Jan;221(1):206-16. doi: 10.1016/j.expneurol.2009.10.024. Epub 2009 Nov 10.
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.
脊髓损伤后的功能恢复仍然是一个重要的目标。损伤脊髓中抑制性分子的存在和适当许可因子的缺乏导致纤维束的重新连接和功能失败。中枢神经系统损伤的啮齿动物和灵长类动物模型的实验性移植导致这样一种观点，即许旺细胞（SCs）是自体移植以协助病变部位髓鞘形成和在中枢神经系统中递送治疗剂的有前途的候选物。在这项研究中，我们使用逆转录病毒转导来遗传修饰来自 GFP-转基因小鼠的SCs，以过表达细胞粘附分子 L1，该蛋白促进神经突生长并与髓鞘形成有关。表达 L1 或其嵌合分泌形式 L1-Fc 的 SCs 被混合并在成年小鼠脊髓压迫损伤后立即移植到损伤部位的前方。我们的结果表明，与接受转导对照载体或根本没有细胞的动物相比，手术后 3 周，但不是此后，移植了表达 L1/L1-Fc 的 SCs 的小鼠表现出更快的运动功能恢复。形态学分析表明，加速的功能恢复与移植的和宿主的 SCs 的更早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 5-羟色胺能纤维向损伤部位内和穿过损伤部位的发芽增加。我们的结果表明，移植过表达 L1 的 SCs 增强了损伤后脊髓修复的早期事件，并且可以与其他促进再生的分子一起考虑用于组合策略。
