Spinal cord injury (SCI) is a highly debilitating pathology without curative treatment. One of the most promising disease modifying strategies consists in the implantation of stem cells to reduce inflammation and promote neural regeneration. In the present study we tested a new human bone marrow-derived stromal cell preparation (bmSC) as a therapy of SCI. Spinal cord contusion injury was induced in adult male rats at thoracic level T9/T10 using the Infinite Horizon impactor. One hour after lesion the animals were treated with a sub-occipital injection of human bmSC into the cisterna magna. No immune suppression was used. One dose of bmSC consisted, on average, of 2.3 million non-manipulated cells in 100 μL suspension, which was processed out of fresh human bone marrow from the iliac crest of healthy volunteers. Treatment efficacy was compared with intraperitoneal injections of methylprednisolone (MP) and saline. The recovery of motor functions was assessed during a surveillance period of nine weeks. Adverse events as well as general health, weight and urodynamic functions were monitored daily. After this time, the animals were perfused, and the spinal cord tissue was investigated histologically. Rats treated with bmSC did not reject the human implants and showed no sign of sickness behavior or neuropathic pain. Compared to MP treatment, animals displayed better recovery of their SCI-induced motor deficits. There were no significant differences in the recovery of bladder control between groups. Histological analysis at ten weeks after SCI revealed no differences in tissue sparing and astrogliosis, however, bmSC treatment was accompanied with reduced axonal degeneration in the dorsal ascending fiber tracts, lower Iba1-immunoreactivity (IR) close to the lesion site and reduced apoptosis in the ventral grey matter. Neuroinflammation, as evidenced by CD68-IR, was significantly reduced in the MP-treated group. Human bmSC that were prepared by negative selection without expansion in culture have neuroprotective properties after SCI. Given the effect size on motor function, implantation in the acute phase was not sufficient to induce spinal cord repair. Due to their immune modulatory properties, allogeneic implants of bmSC can be used in combinatorial therapies of SCI.

中文翻译：

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使用阴性选择制备的人骨髓源性基质细胞治疗脊髓损伤大鼠。

脊髓损伤（SCI）是一种高度衰弱的病理，无需治疗。最有希望的疾病改变策略之一是植入干细胞以减少炎症并促进神经再生。在本研究中，我们测试了一种新的人类骨髓源基质细胞制剂（bmSC）作为SCI的疗法。使用无限地平线撞击器在成年雄性大鼠的胸椎水平T9 / T10处诱发脊髓挫伤。损伤后一小时，通过枕后向人大池中注射人bmSC治疗动物。没有使用免疫抑制。一剂bmSC平均由100μL悬浮液中的230万个未处理的细胞组成，这些细胞是从健康志愿者的c中提取的新鲜人骨髓中制成的。将治疗效果与腹膜内注射甲基强的松龙（MP）和盐水进行比较。在九周的监视期内评估了运动功能的恢复情况。每天监测不良事件以及总体健康状况，体重和尿动力功能。此后，对动物进行灌注，并组织学检查脊髓组织。用bmSC治疗的大鼠没有排斥人体植入物，也没有表现出疾病行为或神经性疼痛的迹象。与MP处理相比，动物表现出了更好的SCI诱导的运动缺陷恢复。两组之间膀胱控制的恢复没有显着差异。SCI十周后的组织学分析显示，组织保留和星形胶质增生没有差异。bmSC治疗伴随着背侧上升纤维束中轴突变性的减少，病变部位附近的Iba1免疫反应性（IR）的降低以及腹灰质细胞凋亡的减少。MP治疗组的CD68-IR证明神经炎症明显减少。通过阴性选择在培养中不扩增而制备的人bmSC具有SCI后的神经保护特性。考虑到对运动功能的影响大小，急性期植入不足以诱导脊髓修复。由于其免疫调节特性，bmSC的同种异体植入物可用于SCI的组合治疗。如CD68-IR所证明，在MP治疗组中显着降低。通过阴性选择在培养中不扩增而制备的人bmSC具有SCI后的神经保护特性。考虑到对运动功能的影响大小，急性期植入不足以诱导脊髓修复。由于其免疫调节特性，bmSC的同种异体植入物可用于SCI的组合治疗。如CD68-IR所证明，在MP治疗组中显着降低。通过阴性选择在培养中不扩增而制备的人bmSC具有SCI后的神经保护特性。考虑到对运动功能的影响大小，急性期植入不足以诱导脊髓修复。由于其免疫调节特性，bmSC的同种异体植入物可用于SCI的组合治疗。