Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis.
Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis.
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DOI：
10.1371/journal.pone.0003145
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发表时间：
2008-09-05
期刊：
影响因子：
3.7
通讯作者：
Ben-Hur T
中科院分区：
文献类型：
--
作者：
Aharonowiz M;Einstein O;Fainstein N;Lassmann H;Reubinoff B;Ben-Hur T
多发性硬化（MS）是一种免疫介导的中枢神经系统（CNS）脱髓鞘疾病。MS的一种潜在的新治疗方法是细胞移植，其可以促进髓鞘再生并抑制炎症过程。我们将人胚胎干细胞（hESC）衍生的早期多能神经前体细胞（NPs）移植到MS动物模型实验性自身免疫性脑脊髓炎（EAE）诱导的小鼠脑室中。我们研究了移植NPs对疾病的功能和病理表现的影响。移植的hESC衍生的NP显著减少了EAE的临床体征。组织学检查显示移植的NPs迁移到宿主白色物质，然而，分化为成熟的少突胶质细胞和髓鞘再生可以忽略不计。CNS炎症和组织损伤的演变和进展的时程分析显示，移植动物的炎症过程减弱，这与轴突损伤和脱髓鞘的减少相关。共培养实验表明，hESC衍生的NP抑制淋巴结衍生的T细胞的活化和增殖，以响应非特异性多克隆刺激。移植的治疗效果与移植物或宿主的髓鞘再生无关，而是由免疫抑制性神经保护机制介导的。这里证明的hESC衍生的NP对EAE的减弱可以作为进一步开发hESC用于MS细胞治疗的第一步。
Multiple sclerosis (MS) is an immune mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination and suppress the inflammatory process. We transplanted human embryonic stem cells (hESC)-derived early multipotent neural precursors (NPs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted NPs on the functional and pathological manifestations of the disease. Transplanted hESC-derived NPs significantly reduced the clinical signs of EAE. Histological examination showed migration of the transplanted NPs to the host white matter, however, differentiation to mature oligodendrocytes and remyelination were negligible. Time course analysis of the evolution and progression of CNS inflammation and tissue injury showed an attenuation of the inflammatory process in transplanted animals, which was correlated with the reduction of both axonal damage and demyelination. Co-culture experiments showed that hESC-derived NPs inhibited the activation and proliferation of lymph node–derived T cells in response to nonspecific polyclonal stimuli. The therapeutic effect of transplantation was not related to graft or host remyelination but was mediated by an immunosuppressive neuroprotective mechanism. The attenuation of EAE by hESC-derived NPs, demonstrated here, may serve as the first step towards further developments of hESC for cell therapy in MS.
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影响因子：
3.3
作者：
Ben-Hur, Tamir;van Heeswijk, Ruud B.;Bulte, Jeff W. M.
通讯作者：
Bulte, Jeff W. M.
影响因子：
4.8
作者：
Hemmer, B;Cepok, S;Sommer, N
通讯作者：
Sommer, N
影响因子：
3.5
作者：
Einstein, O;Karussis, D;Ben-Hur, T
通讯作者：
Ben-Hur, T
影响因子：
2.5
作者：
GUY, J;ELLIS, EA;HOPE, GM
通讯作者：
HOPE, GM
影响因子：
158.5
作者：
Trapp, BD;Peterson, J;Bö, L
通讯作者：
Bö, L