Xiao Ming, Klueber Kathleen M, Guo Zhanfang, Lu Chengliang, Wang Heming, Roisen Fred J
Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China.
Neurobiol Dis. 2007 May;26(2):363-74. doi: 10.1016/j.nbd.2007.01.012. Epub 2007 Feb 9.
We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater functional recovery of forelimb use during the 12 weeks after NSFCs engraftment than in the control rats. Anterograde tracing with biotinylated dextran amine (BDA) confirmed the presence of RST axons within the white matter 4-8 segments caudal to the grafts. Both immunofluorescence and immunoelectron microscopy revealed the BDA-labeled RST axonal terminals reestablished synaptic connections with motoneurons in the ventral horn of the distal cervical spinal cord. Further study of forelimb functional recovery in NSFCs-engrafted subgroups considered the effects of a second dorsolateral funiculotomy, irreversibly destroying the recovery, and the injection of muscimol, blocking RST neuronal activity reversibly. These results highlight the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous cell source for spinal cord repair.
我们研究了移植的人成年嗅神经上皮神经球形成细胞(NSFCs)对部分颈髓半切术后红核脊髓束(RST)轴突再生和再支配以及运动恢复的影响,该手术完全切断了RST。每周进行的行为测试表明,与对照大鼠相比,NSFCs移植后12周内前肢使用功能恢复得更好。用生物素化葡聚糖胺(BDA)进行的顺行示踪证实,在移植部位尾侧4-8节段的白质中有RST轴突存在。免疫荧光和免疫电子显微镜检查均显示,BDA标记的RST轴突终末与颈髓远端腹角的运动神经元重新建立了突触连接。对NSFCs移植亚组前肢功能恢复的进一步研究考虑了第二次背外侧索切断术的影响,该手术不可逆地破坏了恢复情况,以及注射蝇蕈醇,其可逆地阻断RST神经元活动。这些结果突出了人嗅神经上皮来源的祖细胞作为脊髓修复自体细胞来源的独特潜力。