Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.
Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.
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DOI：
10.1038/s41467-017-02613-x
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发表时间：
2018-01-08
影响因子：
16.6
通讯作者：
Tuszynski MH
中科院分区：
文献类型：
--
作者：
Dulin JN;Adler AF;Kumamaru H;Poplawski GHD;Lee-Kubli C;Strobl H;Gibbs D;Kadoya K;Fawcett JW;Lu P;Tuszynski MH
神经前体细胞（NPC）移植在神经系统疾病中具有很高的治疗潜力。功能的恢复可能依赖于宿主和移植物之间相互连接的形成。虽然已经报道了从脑中的神经移植物延伸出的轴突在表型上适当的宿主靶区域上形成接触，但尚不清楚再生为NPC移植物的成年受损宿主轴突是否也形成适当的连接。我们报道了移植到损伤的成年大鼠脊髓中的脊髓NPC自组装器官型背角样结构域。这些簇被再生的成年宿主感觉轴突广泛支配，并且被皮质脊髓轴突避开。此外，宿主轴突再生到移植物中在用适当的神经元靶标富集后显著增加。总之，这些发现表明，损伤的成年轴突保留了识别适当靶点的能力，并避免神经祖细胞移植物中的不适当靶点，这表明SCI后复杂电路的恢复是可以实现的。了解移植细胞如何与宿主神经系统相互作用对于基于细胞的神经再生方法将是重要的。在这里，作者研究了移植到受损脊髓的神经祖细胞移植物的感觉命运，并表明宿主轴突保留了区分适当和不适当的移植靶点的能力。
Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it has been reported that axons extending out of neural grafts in the brain form contacts onto phenotypically appropriate host target regions, it is not known whether adult, injured host axons regenerating into NPC grafts also form appropriate connections. We report that spinal cord NPCs grafted into the injured adult rat spinal cord self-assemble organotypic, dorsal horn-like domains. These clusters are extensively innervated by regenerating adult host sensory axons and are avoided by corticospinal axons. Moreover, host axon regeneration into grafts increases significantly after enrichment with appropriate neuronal targets. Together, these findings demonstrate that injured adult axons retain the ability to recognize appropriate targets and avoid inappropriate targets within neural progenitor grafts, suggesting that restoration of complex circuitry after SCI may be achievable. Understanding how transplanted cells interact with the host nervous system will be important for cell based neural regeneration approaches. Here, the authors study the sensory fate of neural progenitor cell grafts transplanted to the injured spinal cord, and show that host axons retain the ability to distinguish appropriate and inappropriate graft targets.
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影响因子：
25
作者：
Gaillard, Afsaneh;Prestoz, Laetitia;Jaber, Mohamed
通讯作者：
Jaber, Mohamed
影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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