Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury.

Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury.
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DOI:
10.1371/journal.pone.0007706
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发表时间:
2009-11-06
期刊:
影响因子:
3.7
通讯作者:
Okano H
Okano H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kumagai G;Okada Y;Yamane J;Nagoshi N;Kitamura K;Mukaino M;Tsuji O;Fujiyoshi K;Katoh H;Okada S;Shibata S;Matsuzaki Y;Toh S;Toyama Y;Nakamura M;Okano H

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亚急性期脊髓损伤(SCI)后移植神经干细胞/祖细胞(NS/PC)可促进啮齿动物模型的功能恢复。然而,治疗脊髓损伤最有效的细胞类型尚不清楚。利用我们最近建立的ES细胞来源的NS/PC培养系统,在该系统中,初级神经球(PNS)和传代的次级神经球(SNS)分别具有神经源性和胶质源性潜能,在这里,我们研究了移植神经源性和胶质源性NS/PC对小鼠脊髓损伤模型功能恢复的不同影响。挫伤后9d移植于Th10水平的胚胎干细胞来源的三叉神经节和三叉神经节细胞分别表现出神经分化和神经胶质分化的趋势,与体外观察到的相似。有趣的是,移植胶质源性SN,而不是神经源性PNS,促进了轴突生长、重新髓鞘形成和血管生成,并导致脊髓损伤后显著的运动功能恢复。这些发现表明,神经胶质源性NS/PC对促进脊髓损伤后的恢复是有效的,并为细胞移植导致脊髓损伤后功能改善的机制提供了重要的见解。
Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.
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