The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue
The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue
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DOI：
10.1038/nbt751
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发表时间：
2002-11-01
影响因子：
46.9
通讯作者：
Snyder, EY
中科院分区：
文献类型：
--
作者：
Park, KI;Teng, YD;Snyder, EY
缺氧缺血性损伤是以广泛组织损失为特征的损伤的原型。将神经干细胞（NSC）接种到聚合物支架上，然后将其植入因缺氧缺血损伤的小鼠大脑的梗死腔中，使我们能够观察到 NSC 与广泛受损的大脑之间自发发生的多重相互作用：实质损失显着减少，实质损失是由宿主和小鼠的许多高度树状神经突组成的复杂网络。 供体来源的神经元出现，并且一些解剖学连接似乎被重建。 NSC-支架复合体改变了宿主皮质神经突的轨迹和复杂性。相反，供体来源的神经元似乎能够在没有特定的外部指令、诱导或对宿主大脑或供体细胞进行基因操作的情况下，定向、适合目标的神经突生长（将轴突延伸到相反的半球）。这些“生物桥”似乎通过促进 NSC 和宿主之间的一系列相互相互作用来揭示或增强组成性修复反应，包括促进神经元分化、增强神经过程的精细化、促进皮质组织的重建和促进连通性。炎症和疤痕也减少了，有利于重建。
Hypoxic-ischemic injury is a prototype for insults characterized by extensive tissue loss. Seeding neural stem cells (NSCs) onto a polymer scaffold that was subsequently implanted into the infarction cavities of mouse brains injured by hypoxia-ischemia allowed us to observe the multiple reciprocal interactions that spontaneously ensue between NSCs and the extensively damaged brain: parenchymal loss was dramatically reduced, an intricate meshwork of many highly arborized neurites of both host- and donor-derived neurons emerged, and some anatomical connections appeared to be reconstituted. The NSC-scaffold complex altered the trajectory and complexity of host cortical neurites. Reciprocally, donor-derived neurons were seemingly capable of directed, target-appropriate neurite outgrowth (extending axons to the opposite hemisphere) without specific external instruction, induction, or genetic manipulation of host brain or donor cells. These "bio-bridges" appeared to unveil or augment a constitutive reparative response by facilitating a series of reciprocal interactions between NSC and host, including promoting neuronal differentiation, enhancing the elaboration of neural processes, fostering the re-formation of cortical tissue, and promoting connectivity. Inflammation and scarring were also reduced, facilitating reconstitution.