1 Institut de Neurophysiopathologie, Aix-Marseille Université , Marseille, France .
2 IRSEA, Research Institute in Semiochemistry and Applied Ethology , Apt, France .
J Neurotrauma. 2018 Aug 1;35(15):1765-1780. doi: 10.1089/neu.2017.5383. Epub 2018 Apr 30.
The transplantation of olfactory ecto-mesenchymal stem cells (OEMSCs) could be a helpful therapeutic strategy for spinal cord repair. Using an acute rat model of high cervical contusion that provokes a persistent hemidiaphragmatic and foreleg paralysis, we evaluated the therapeutic effect of a delayed syngeneic transplantation (two days post-contusion) of OEMSCs within the injured spinal cord. Respiratory function was assessed using diaphragmatic electromyography and neuroelectrophysiological recordings of phrenic nerves (innervating the diaphragm). Locomotor function was evaluated using the ladder-walking locomotor test. Cellular reorganization in the injured area was also studied using immunohistochemical and microscopic techniques. We report a substantial improvement in breathing movements, in activities of the ipsilateral phrenic nerve and ipsilateral diaphragm, and also in locomotor abilities four months post-transplantation with nasal OEMSCs. Moreover, in the grafted spinal cord, axonal disorganization and inflammation were reduced. Some grafted stem cells adopted a neuronal phenotype, and axonal sparing was observed in the injury site. The therapeutic effect on the supraspinal command is presumably because of both neuronal replacements and beneficial paracrine effects on the injury area. Our study provides evidence that nasal OEMSCs could be a first step in clinical application, particularly in patients with reduced breathing/locomotor movements.
嗅外胚间充质干细胞（OEMSCs）的移植可能是一种有助于脊髓修复的治疗策略。我们使用急性高位颈挫伤大鼠模型，该模型可导致膈肌和前肢持续瘫痪，评估了在受伤的脊髓内延迟同种异体 OEMSCs 移植（挫伤后两天）的治疗效果。使用膈神经的膈肌肌电图和神经电生理记录评估呼吸功能（支配膈肌）。使用梯级行走运动测试评估运动功能。还使用免疫组织化学和显微镜技术研究了损伤区域的细胞重组。我们报告说，移植鼻 OEMSCs 四个月后，呼吸运动、同侧膈神经和同侧膈肌的活动以及运动能力有了显著改善。此外，在移植的脊髓中，轴突紊乱和炎症减少。一些移植的干细胞表现出神经元表型，并且在损伤部位观察到轴突保留。对中枢神经系统的治疗效果可能是由于神经元替代和对损伤区域的有益旁分泌作用。我们的研究提供了证据，表明鼻 OEMSCs 可能是临床应用的第一步，特别是对于呼吸/运动功能降低的患者。
