Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas
Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas
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DOI：
10.1073/pnas.97.23.12846
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发表时间：
2000-11-07
影响因子：
11.1
通讯作者：
Snyder, EY
中科院分区：
文献类型：
--
作者：
Aboody, KS;Brown, A;Snyder, EY
脑肿瘤(如胶质瘤)治疗的障碍之一是肿瘤的扩张程度，渗透到周围组织，并广泛迁移到正常大脑，通常使它们难以得到有效的切除、放疗、化疗或基因治疗。我们证明，当神经干细胞(NSCs)被移植到成年啮齿动物体内的实验性脑胶质瘤中时，它们会迅速而广泛地分布在整个肿瘤床上，并以独特的方式并列迁移到广泛扩张和积极推进的肿瘤细胞中，同时继续稳定地表达外源基因。神经干细胞“包围”侵袭的肿瘤边界，同时“追逐”浸润性的肿瘤细胞。当移植到远离肿瘤的部位(如正常组织、对侧大脑半球或脑室)时，供体细胞可通过靶向肿瘤细胞(包括人脑胶质母细胞瘤)的正常组织迁移。当被植入中枢神经系统外的血管内。神经干细胞将以颅内肿瘤为靶点。神经干细胞可以提供一种与治疗相关的分子-胞嘧啶脱氨酶-这样就可以量化地减少肿瘤负担。这些数据表明，固有的迁移性神经干细胞作为靶向治疗基因和载体的载体用于难治性、迁移性、侵袭性脑肿瘤的辅助使用。更广泛地说，他们认为神经干细胞的迁移可以是广泛的，即使是在成人的大脑中和沿着非刻板印象的路线，如果病理(这里以肿瘤为模型)存在的话。
One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them "elusive" to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs "surround" the invading tumor border while "chasing down" infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly. NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule-cytosine deaminase-such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present.