Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury.
Engrafted Neural Stem/Progenitor Cells Promote Functional Recovery through Synapse Reorganization with Spared Host Neurons after Spinal Cord Injury.
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DOI：
10.1016/j.stemcr.2015.06.004
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发表时间：
2015-08-11
影响因子：
5.9
通讯作者：
Okada S
中科院分区：
文献类型：
--
作者：
Yokota K;Kobayakawa K;Kubota K;Miyawaki A;Okano H;Ohkawa Y;Iwamoto Y;Okada S
神经干细胞/祖细胞(NSPC)移植是治疗脊髓损伤(SCI)的一种有前景的治疗策略。然而，NSPC移植治疗严重脊髓损伤的疗效尚不清楚。我们在这里表明，NSPC移植促进了轻、中度脊髓损伤后的功能恢复，但不能促进严重脊髓损伤后的功能恢复。在严重脊髓损伤小鼠中，在NSPC植入范围内几乎没有剩余的宿主神经元；因此，我们检查了移植和宿主的共同分布是否是功能改善的贡献因素。激光显微切割的细胞选择性分析显示，药物诱导的宿主神经元消融显著降低了移植的NSPC的突触生成潜力。此外，在宿主神经元消融后，神经元逆行追踪显示NSPC移植后桥接病变的固有脊髓中继连接较少。我们的研究结果表明，移植的NSPC和备用宿主神经元之间的交互突触重组对于功能恢复至关重要，这为制定严重脊髓损伤的治疗策略提供了重要的见解。NSPC移植对严重脊髓损伤后的功能恢复几乎没有影响宿主神经元消融甚至对中度SCI也否定了移植的效果激光显微解剖揭示了移植的NSPC体内的突触形成情况NSPC通过突触发生促进神经回路的重组在本文中，Okada和他的同事们展示了脊髓损伤后神经干细胞/祖细胞移植改善功能的机制。他们通过激光显微解剖(LMD)阐明了移植的NSPC的详细的突触发生情况，并证明了损伤的NSPC通过移植的NSPC与备用宿主神经元之间的突触发生而重组。
Neural stem/progenitor cell (NSPC) transplantation is a promising therapeutic strategy for spinal cord injury (SCI). However, the efficacy of NSPC transplantation on severe SCI is poorly understood. We herein show that NSPC transplantation promotes functional recovery after mild and moderate SCI, but not after severe SCI. In severe SCI mice, there were few remaining host neurons within the range of NSPC engraftment; thus, we examined whether the co-distribution of transplant and host is a contributory factor for functional improvement. A cellular selective analysis using laser microdissection revealed that drug-induced host neuronal ablation considerably decreased the synaptogenic potential of the engrafted NSPCs. Furthermore, following host neuronal ablation, neuronal retrograde tracing showed less propriospinal relay connections bridging the lesion after NSPC transplantation. Our findings suggest that the interactive synaptic reorganization between engrafted NSPCs and spared host neurons is crucial for functional recovery, providing significant insight for establishing therapeutic strategies for severe SCI. NSPC transplantation has almost no effect on the functional recovery after severe SCI Host neuronal ablation negates the efficacy of transplantation even for moderate SCI Laser microdissection reveals the in vivo synaptogenic profiles of engrafted NSPCs Engrafted NSPCs promote the reorganization of neural circuits through synaptogenesis In this article, Okada and colleagues show a mechanism underlying the functional improvement by neural stem/progenitor cell (NSPC) transplantation after spinal cord injury. They clarify the detailed synaptogenic profiles of the engrafted NSPCs by laser microdissection (LMD), and they demonstrate that the injured propriospinal circuit is reorganized through synaptogenesis between the engrafted NSPCs and the spared host neurons.