Hospital Nacional de Parapléjicos, c/Finca la Peraleda, 45071, Toledo, Spain.
School of Mental Health and Neuroscience and EURON Graduate School of Neuroscience, Maastricht University, Universiteitssingel 40, 6229ER, Maastricht, Netherlands.
J Biomed Sci. 2020 Feb 18;27(1):35. doi: 10.1186/s12929-020-00629-y.
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.
脊髓损伤（SCI）是一种高度致残的疾病，目前尚无治愈方法。最有前途的疾病修饰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骨髓基质细胞制剂（bmSC）作为 SCI 的治疗方法。
在成年雄性大鼠 T9/T10 胸椎水平使用无限地平线撞击器诱导脊髓挫伤损伤。损伤后 1 小时，通过枕下注射将人 bmSC 注入枕骨大孔。未使用免疫抑制。一次 bmSC 剂量平均由 100μL 悬浮液中的 230 万个未经处理的细胞组成，这些细胞是从健康志愿者髂嵴的新鲜人骨髓中加工而来的。治疗效果与腹腔注射甲基强的松龙（MP）和生理盐水进行了比较。在 9 周的监测期间评估运动功能的恢复情况。每天监测不良事件以及一般健康状况、体重和尿动力学功能。经过这段时间后，对动物进行灌注，并对脊髓组织进行组织学研究。
接受 bmSC 治疗的大鼠不排斥人植入物，也没有表现出病态行为或神经病理性疼痛的迹象。与 MP 治疗相比，动物的 SCI 诱导运动缺陷恢复更好。各组间膀胱控制的恢复无显著差异。SCI 后 10 周的组织学分析显示，在组织保存和星形胶质增生方面无差异，然而，bmSC 治疗伴有背侧上行纤维束中的轴突变性减少、损伤部位附近的 Iba1 免疫反应（IR）降低和腹侧灰质中的细胞凋亡减少。MP 治疗组的神经炎症，如 CD68-IR 所示，显著减少。
未经培养的阴性选择制备的人 bmSC 在 SCI 后具有神经保护作用。考虑到对运动功能的影响大小，在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。
