Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Neuroscience Institute of Turin, Italy.
J Neurosurg Spine. 2011 Jul;15(1):97-106. doi: 10.3171/2011.1.SPINE10607. Epub 2011 Apr 1.
Spinal cord injury (SCI) often results in irreversible and permanent neurological deficits below the injury site and is considered a pathological state of functional damage to local neurons and axon fibers. There are several experimental treatments to minimize tissue damage, and recently cell transplantation has emerged as a promising approach in spinal cord repair. The authors undertook this study to evaluate grafting of neural tube precursors as a possible therapeutic strategy in a model of spinal cord compression in the mouse.
Compression SCI was induced at the T-13 level in adult male mice. Immediately after injury, neural precursor cells (NPs) were transplanted into the SCI lesion cavity in 18 mice; the remaining 19 mice received saline injections into the lesion cavity and were used as controls. Spinal cords were examined 12, 19, and 26 days postinjury to investigate the survival of the NPs and their effects on the cellular environment, glial scar and glial cyst formation, astrogliosis, and microglial activation.
Grafted NPs survived well and integrated into the host spinal cord tissue. Some NPs had differentiated into cells expressing glial and neuronal markers at all 3 end points. Analysis of glial cyst volume showed a lesion volume reduction of 63.2% in the NP-treated mice compared with volume in the injured but untreated mice. There appeared to be no difference in astroglial and microglial activation between untreated mice and treated ones. Sensory and motor tests demonstrated that transplantation of NPs promoted improvement in injured and treated animals compared with controls.
These results support the therapeutic potential of NPs, demonstrating that they can survive for a long time, differentiate, integrate into the injured spinal cord, and promote functional recovery after SCI.
脊髓损伤(SCI)常导致损伤部位以下不可逆和永久性神经功能缺损,被认为是局部神经元和轴突纤维功能损伤的病理状态。有几种实验性治疗方法可以最大限度地减少组织损伤,最近细胞移植已成为脊髓修复的一种有前途的方法。作者进行这项研究是为了评估神经管前体细胞移植作为一种治疗策略在小鼠脊髓压迫模型中的可能性。
成年雄性小鼠 T-13 水平诱导压迫性 SCI。损伤后立即将神经前体细胞(NPs)移植到 SCI 损伤腔内,18 只小鼠接受移植;其余 19 只小鼠接受损伤腔内生理盐水注射作为对照。在损伤后 12、19 和 26 天检查脊髓,以研究 NPs 的存活及其对细胞环境、胶质瘢痕和胶质囊肿形成、星形胶质细胞增生和小胶质细胞激活的影响。
移植的 NPs 存活良好并整合到宿主脊髓组织中。一些 NPs 在所有 3 个终点都分化为表达神经胶质和神经元标记物的细胞。对神经胶质囊肿体积的分析表明,与未治疗的损伤小鼠相比,NP 治疗组的病变体积减少了 63.2%。未治疗小鼠和治疗小鼠之间的星形胶质细胞和小胶质细胞激活似乎没有差异。感觉和运动测试表明,与对照组相比,NP 移植促进了受伤和治疗动物的功能恢复。
这些结果支持 NPs 的治疗潜力,表明它们可以长期存活、分化、整合到损伤的脊髓中,并促进 SCI 后的功能恢复。