Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
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DOI：
10.1038/srep10666
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发表时间：
2015-06-08
影响因子：
4.6
通讯作者：
Kozlova, Elena N.
中科院分区：
文献类型：
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作者：
Hoeber, Jan;Trolle, Carl;Kozlova, Elena N.
由于周围神经系统和中枢神经系统之间的断开，背根撕脱导致感觉功能永久性损伤。因此，需要改进策略将受伤的感觉神经元与其脊髓目标重新连接，以便在臂丛和腰骶丛撕脱伤后实现功能修复。在这里，我们表明，如果通过人类神经祖细胞（hNP）移植将撕脱的感觉纤维与脊髓桥接，成年小鼠的感觉功能可以恢复。移植动物对外周机械感觉刺激的反应显着改善。跨神经节追踪显示宿主感觉轴突仅存在于接受治疗的动物的脊髓背角中。免疫组织化学分析证实，感觉纤维已经通过桥生长，并显示出移植物的强大存活和分化能力。移植物远端的修复背根部分完全消除了行为改善。这表明hNP移植促进背根撕脱后感觉运动功能的恢复，并且这些作用是由宿主感觉轴突的脊柱向内生长介导的。这些结果为开发基于干细胞的新型策略提供了理论依据，以在功能上有效地桥接周围和中枢神经系统。
Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.