Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis

Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis
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DOI:
10.1016/j.mcn.2003.08.009
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发表时间:
2003-12-01
影响因子:
3.5
通讯作者:
Ben-Hur, T
Ben-Hur, T
中科院分区:
医学3区
文献类型:
--
作者:
Einstein, O;Karussis, D;Ben-Hur, T

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脑移植神经前体细胞可促进中枢神经系统的再生。由于大多数急性中枢神经系统疾病的发病机制涉及炎症成分,我们研究了鼻咽癌移植是否会影响脑部炎症。将新生大鼠多潜能神经干细胞移植到弥漫性脑炎症模型急性实验性变态反应性脑脊髓炎(EAE)大鼠体内。细胞迁移到炎症的白质中,并分化为神经胶质细胞。鼻咽癌移植减轻了EAE的临床严重程度和脑部炎症,表现为血管周围浸润物减少,ICAM-1和LFA-1表达减少。在体外,NPC抑制EAE大鼠来源淋巴细胞的基础增殖和对刀豆球蛋白A和MOG多肽的增殖反应。纯化的星形胶质细胞在体外抑制淋巴细胞增殖,但不能在体内迁移到EAE脑内,也不能降低EAE的严重程度或脑部炎症。因此,移植的神经干细胞通过一种抗炎机制减轻急性EAE,这种机制依赖于细胞迁移到炎症脑组织的能力。(C)2003 Elsevier Inc.保留所有权利。
Brain transplantation of neural precursor cells (NPCs) has been proposed to enhance CNS regeneration. As the pathogenesis of most acute CNS diseases involves an inflammatory component, we studied whether NPC transplantation affects brain inflammation. Newborn rat multipotential NPCs were transplanted intraventriculary into acute experimental allergic encephalomyelitis (EAE) rats, a model for disseminated brain inflammation. Cells migrated into inflamed white matter and differentiated into glial cells. NPC transplantation attenuated the clinical severity of EAE and the brain inflammation, indicated by reduction in perivascular infiltrates and decreased expression of ICAM-1 and LFA-1. NPCs inhibited basal proliferation and proliferative responses to Concavalin-A and to MOG peptide of EAE rat-derived lymphocytes in vitro. Purified astrocytes inhibited lymphocyte proliferation in vitro, but did not migrate into EAE brains in vivo, and did not reduce EAE severity or brain inflammation. Thus, transplanted NPCs attenuate acute EAE via an anti-inflammatory mechanism which depends on cell ability to migrate into inflamed brain tissue. (C) 2003 Elsevier Inc. All rights reserved.