Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner

Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner
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DOI:
10.1016/j.neulet.2007.08.048
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发表时间:
2007-10-16
影响因子:
2.5
通讯作者:
Yoshida, Jun
Yoshida, Jun
中科院分区:
医学4区
文献类型:
--
作者:
Takeuchi, Hiroki;Natsume, Atsushi;Yoshida, Jun

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神经干细胞(NSC)移植在脊髓损伤中显示出相当大的治疗潜力。然而,大多数动物实验都是通过将这些细胞直接注射到受伤的脊髓中进行的。NSCs的一个主要特征是它们通过神经系统的特殊迁移能力。基于NSCs的迁移能力,我们研究了微创静脉输送NSCs是否能促进其向损伤脊髓的迁移,并鉴定了病变分泌的化学引诱剂。在T8水平脊髓受压3、7和10天后,给裸鼠静脉注射标记的人NSCs。损伤后第7天,NSCs向损伤脊髓的迁移量最大;这与病变中肝细胞生长因子和基质细胞衍生因子-1 mRNA表达的峰值相关,但与血脑屏障的破坏无关。最后,移植的NSCs在移植21天后分化为神经元亚群和胶质亚群。我们的研究表明,静脉注射的NSCs可以作为一种可再生来源,用于替代脊髓损伤治疗中丢失的细胞。2007爱思唯尔爱尔兰有限公司版权所有。
Neural stem cell (NSC) transplantation has exhibited considerable therapeutic potential in spinal cord injury. However, most experiments in animals have been performed by injecting these cells directly into the injured spinal cord. A cardinal feature of NSCs is their exceptional migratory ability through the nervous system. Based on the migratory ability of NSCs, we investigated whether minimally invasive intravenous delivery of NSCs could facilitate their migration to the injured spinal cord and identified the chemo-attractants secreted by the lesions. Nude mice were injected intravenously with labelled human NSCs at 3, 7 and 10 days after the compression of the spinal cord at the T8 level. The migration of NSCs to the lesioned spinal cord was highest at 7 days after injury; this correlated with the peak of hepatocyte growth factor and stromal cell-derived factor-1 mRNA expressions in the lesion but not with the disruption of the blood-brain barrier. Finally, the grafted NSCs differentiated into neuronal and glial subpopulations at 21 days after transplantation. Our study suggests that intravenously administered NSCs can be employed as a renewable source for replacing lost cells for the treatment of spinal cord injuries. (c) 2007 Elsevier Ireland Ltd. All rights reserved.