Subventricular Zone-Derived Neural Progenitor Cells Migrate Along a Blood Vessel Scaffold Toward the Post-stroke Striatum
Subventricular Zone-Derived Neural Progenitor Cells Migrate Along a Blood Vessel Scaffold Toward the Post-stroke Striatum
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DOI：
10.1002/stem.306
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发表时间：
2010-03-31
期刊：
影响因子：
5.2
通讯作者：
Sawamoto, Kazunobu
中科院分区：
文献类型：
--
作者：
Kojima, Takuro;Hirota, Yuki;Sawamoto, Kazunobu
成年人大脑的脑室下区（SVZ）含有神经干细胞，这些细胞在各种损伤后具有再生新神经元的能力。脑缺血引起脑组织损伤并诱导神经再生以及血管生成。我们以前报道过，小鼠缺血性损伤后，SVZ衍生的神经祖细胞（NPC）迁移到纹状体，这些NPC经常与再生脑组织中的血管相关。在这里，我们更详细地研究了血管在神经再生过程中的作用。BrdU给药实验显示，新产生的NPC与缺血性纹状体中新形成和预先存在的血管相关，表明血管生成环境对神经元-血管相互作用不是必需的。为了观察受损脑组织中迁移的NPC和血管，我们对缺血损伤后培养的脑切片进行了实时成像。在这个系统中，我们在Flk 1-EGFP基因敲入小鼠中病毒标记SVZ衍生的NPC，其中血管用EGFP标记。我们的研究结果提供了直接的证据，SVZ衍生的NPC迁移沿着血管从SVZ向纹状体的缺血区域。迁移NPC的引导过程与血管密切相关，表明这种相互作用为NPC提供了方向性指导。这些发现表明，血管作为NPC向受损脑区迁移的支架发挥着重要作用。干细胞2010; 28：545-554
The subventricular zone (SVZ) of the adult brain contains neural stem cells that have the capacity to regenerate new neurons after various insults. Brain ischemia causes damage to brain tissue and induces neural regeneration together with angiogenesis. We previously reported that, after ischemic injury in mice, SVZ-derived neural progenitor cells (NPCs) migrate into the striatum, and these NPCs are frequently associated with blood vessels in the regenerating brain tissue. Here we studied the role of blood vessels during the neural regeneration in more detail. BrdU administration experiments revealed that newly generated NPCs were associated with both newly formed and pre-existing blood vessels in the ischemic striatum, suggesting that the angiogenic environment is not essential for the neuron-blood vessel interaction. To observe migrating NPCs and blood vessels simultaneously in damaged brain tissue, we performed live imaging of cultured brain slices after ischemic injury. In this system, we virally labeled SVZ-derived NPCs in Flk1-EGFP knock-in mice in which the blood vessels are labeled with EGFP. Our results provide direct evidence that SVZ-derived NPCs migrate along blood vessels from the SVZ toward the ischemic region of the striatum. The leading process of the migrating NPCs was closely associated with blood vessels, suggesting that this interaction provides directional guidance to the NPCs. These findings suggest that blood vessels play an important role as a scaffold for NPCs migration toward the damaged brain region. STEM CELLS 2010; 28: 545-554