White matter tracts for the trafficking of neural progenitor cells characterized by cellular MRI and immunohistology: the role of CXCL12/CXCR4 signaling.

White matter tracts for the trafficking of neural progenitor cells characterized by cellular MRI and immunohistology: the role of CXCL12/CXCR4 signaling.
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以细胞MRI和免疫组织学为特征的神经祖细胞运输的白质道:CXCL12/CXCR4信号的作用。

DOI:
10.1007/s00429-014-0770-4
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发表时间:
2015-07
影响因子:
3.1
通讯作者:
Chang C
Chang C
中科院分区:
医学3区
文献类型:
--
作者:
Chen CC;Hsu YH;Jayaseema DM;Chen JY;Hueng DY;Chang C

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在正常和病理条件下,白质束对于神经祖细胞(NPC)的运输都很重要,但其潜在机制尚不清楚。白质的方向性有利于分子或细胞长距离分布,但这一特征不太可能是有效迁移的唯一原因。本研究假设NPCs向白质的有效迁移受到神经化学吸引力——CXCL12/CXCR4信号传导的影响,这是NPCs靶向迁移的主要机制。为了验证这一观点,本研究调查了胼胝体 (CC) 中施用 CXCL12 对移植的 NPC 迁移行为的影响。采用基于 MRI 和磁性细胞标记技术的活体动物跟踪平台。将 NPC 进行磁性标记,然后移植到 CC 的右端。 CXCL12在左端连续输注。使用 3D 梯度回波 T2* 加权成像在 7 天的过程中反复监测 NPC 的迁移。结果发现,CXCL12 诱导 NPC 从移植物迁移达 1,881 μm,而自发迁移仅为 200 μm。 CXCL12 诱导的迁移速度效率是原来的九倍。结果表明,CXCL12/CXCR4 信号传导可能是 NPC 沿着白质束有效迁移的机制。该研究还提出了一种潜在策略,可促进 NPC 脑部疾病治疗中的靶向迁移。本文的在线版本 (doi:10.1007/s00429-014-0770-4) 包含补充材料,可供授权用户使用。
White matter tracts are important for the trafficking of neural progenitor cells (NPCs) in both normal and pathological conditions, but the underlying mechanism is not clear. The directionality of white matter is advantageous for molecules or cells to distribute over a long distance, but this feature is unlikely solely responsible for efficient migration. The present study hypothesizes that the efficient migration of NPCs into white matter is under the influences of neurochemical attraction—CXCL12/CXCR4 signaling, a major mechanism underlying the targeted migration of NPCs. To test this view, the present study investigated the effects of CXCL12 administration into the corpus callosum (CC) on the migratory behavior of transplanted NPCs. A living animal tracking platform based on MRI and a magnetic cell labeling technique was employed. The NPCs were magnetically labeled and then transplanted at the right end of the CC. CXCL12 was infused continuously at the left end. Migration of NPCs was monitored repeatedly over a 7-day course using 3D gradient echo T2*-weighted imaging. It was found that, CXCL12 induced NPCs to migrate up to 1,881 μm from the graft whereas the spontaneous migration was mere 200 μm. CXCL12 induced migration that was nine times as efficient in the speed. The results indicate that the CXCL12/CXCR4 signaling may be a mechanism via which NPCs efficiently migrate along the white matter tracts. The study also presents a potential strategy for facilitating the targeted migration in NPC therapy for brain disorders. The online version of this article (doi:10.1007/s00429-014-0770-4) contains supplementary material, which is available to authorized users.
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