Hunt Matthew, Lu Paul, Tuszynski Mark H
Dept. of Neurosciences, University of California - San Diego, La Jolla, CA, USA.
Dept. of Neurosciences, University of California - San Diego, La Jolla, CA, USA; Veterans Administration Medical Center, San Diego, CA, USA.
Exp Neurol. 2017 Oct;296:69-73. doi: 10.1016/j.expneurol.2017.07.005. Epub 2017 Jul 8.
Neural progenitor cells (NPCs) grafted to sites of spinal cord injury (SCI) extend numerous axons over long distances and form new synaptic connections with host neurons. In the present study we examined the myelination of axons emerging from NPC grafts. Rat embryonic day 14 (E14) multipotent NPCs constitutively expressing GFP were grafted into adult C5 spinal cord hemisection lesions; 3months later we examined graft-derived axonal diameter and myelination using transmission electron microscopy. 104 graft-derived axons were characterized. Axon diameter ranged from 0.15 to 1.70μm, and 24% of graft-derived axons were myelinated by host oligodendrocytes caudal to the lesion. The average diameter of myelinated axons (0.72±0.3μm) was significantly larger than that of non-myelinated axons (0.61±0.2μm, p<0.05). Notably, the G-ratio of myelinated graft-derived axons (0.77±0.01) was virtually identical to that of the normal, intact spinal cord described in published reports. These findings indicate that axons emerging from early stage neural grafts into the injured spinal cord recapitulate both the small/medium size range and myelin thickness of intact spinal cord axons.
移植到脊髓损伤(SCI)部位的神经祖细胞(NPCs)会长出许多轴突,并与宿主神经元形成新的突触连接。在本研究中,我们检测了NPC移植后长出的轴突的髓鞘形成情况。将组成性表达绿色荧光蛋白(GFP)的大鼠胚胎第14天(E14)多能NPC移植到成年C5脊髓半切损伤处;3个月后,我们使用透射电子显微镜检测移植来源的轴突直径和髓鞘形成情况。对104条移植来源的轴突进行了特征分析。轴突直径范围为0.15至1.70μm,24%的移植来源轴突在损伤部位尾侧被宿主少突胶质细胞髓鞘化。有髓轴突的平均直径(0.72±0.3μm)显著大于无髓轴突(0.61±0.2μm,p<0.05)。值得注意的是,移植来源有髓轴突的G比值(0.77±0.01)与已发表报告中描述的正常完整脊髓的G比值几乎相同。这些发现表明,早期神经移植到损伤脊髓后长出的轴突在大小范围和髓鞘厚度上都重现了完整脊髓轴突的特征。