Regenerating Corticospinal Axons Innervate Phenotypically Appropriate Neurons within Neural Stem Cell Grafts
Regenerating Corticospinal Axons Innervate Phenotypically Appropriate Neurons within Neural Stem Cell Grafts
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DOI：
10.1016/j.celrep.2019.01.099
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发表时间：
2019-02-26
期刊：
影响因子：
8.8
通讯作者：
Tuszynski, Mark H.
中科院分区：
文献类型：
--
作者：
Kumamaru, Hiromi;Lu, Paul;Tuszynski, Mark H.
神经祖细胞移植在脊髓损伤部位形成新的神经传递。利用一组神经元标记，我们证明了鼠类脊髓损伤部位的脊髓祖细胞移植采用不同的脊髓运动和感觉神经元间命运，代表了完整脊髓的大多数神经元亚型，并自发地分离成不同的细胞簇结构域。宿主皮质脊髓运动轴突再生为神经祖细胞移植物，支配适当的运动前中间神经元，基于单纯性疱疹病毒的突触追踪。人类脊髓神经祖细胞移植到非人类灵长类动物也接受了地形合适的皮质脊髓轴突再生。因此，移植的脊髓神经祖细胞产生各种典型的正常脊髓的神经元后代；值得注意的是，再生损伤的成人皮质脊髓运动轴突自发地在异质的、发育中的移植物环境中定位适当的运动域，而不需要额外的外源引导。
Neural progenitor cell grafts form new relays across sites of spinal cord injury (SCI). Using a panel of neuronal markers, we demonstrate that spinal neural progenitor grafts to sites of rodent SCI adopt diverse spinal motor and sensory interneuronal fates, representing most neuronal subtypes of the intact spinal cord, and spontaneously segregate into domains of distinct cell clusters. Host corticospinal motor axons regenerating into neural progenitor grafts innervate appropriate pre-motor interneurons, based on trans-synaptic tracing with herpes simplex virus. A human spinal neural progenitor cell graft to a non-human primate also received topographically appropriate corticospinal axon regeneration. Thus, grafted spinal neural progenitor cells give rise to a variety of neuronal progeny that are typical of the normal spinal cord; remarkably, regenerating injured adult corticospinal motor axons spontaneously locate appropriate motor domains in the heterogeneous, developing graft environment, without a need for additional exogenous guidance.