CEREBROSPINAL FLUID DERIVED FROM PROGRESSIVE MULTIPLE SCLEROSIS PATIENTS PROMOTES NEURONAL AND OLIGODENDROGLIAL DIFFERENTIATION OF HUMAN NEURAL PRECURSOR CELLS IN VITRO
CEREBROSPINAL FLUID DERIVED FROM PROGRESSIVE MULTIPLE SCLEROSIS PATIENTS PROMOTES NEURONAL AND OLIGODENDROGLIAL DIFFERENTIATION OF HUMAN NEURAL PRECURSOR CELLS IN VITRO
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DOI：
10.1016/j.neuroscience.2013.07.022
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发表时间：
2013-10-10
期刊：
影响因子：
3.3
通讯作者：
Sadiq, S. A.
中科院分区：
文献类型：
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作者：
Cristofanilli, M.;Cymring, B.;Sadiq, S. A.
在成年CNS中，组织特异性的脑细胞龛，例如侧脑室的脑室下区和海马齿状回的颗粒下区，含有具有自我更新和分化成功能性脑细胞的能力的多能神经前体细胞（NPC）（Le.神经元、星形胶质细胞或少突胶质细胞）。由于其内在的可塑性，NPC可以被认为是CNS在损伤后试图自我修复的细胞机制的重要组成部分。在炎性CNS疾病中，例如多发性硬化症（MS），神经发生和胶质细胞生成作为“内在”自我修复过程的一部分而发生。然而，在进展性MS中没有实现完全和持久的修复。最近的数据表明，内源性NPC，而试图修复受损的中枢神经系统在MS中，可能成为疾病本身的目标。MS过程中产生的因子，如CNS浸润的血源性炎症单核细胞、反应性CNS驻留细胞和体液介质，可能会改变NPC的生理特性，最终损害其促进神经再生的能力。在这里，我们调查的影响，脑脊液（CSF）来自原发性进行性（PPMS）。和继发性进行性（SPMS）MS患者（CSF MS）对名为ENStem-A的市售人胚胎来源的NPC的存活、增殖和分化的影响。我们发现，与对照CSF相比，PPMS衍生的CSF显著降低了ENStem-A的增殖，并增加了它们向神经元和少突胶质细胞的分化。当用SPMS衍生的CSF处理ENstem-A时，观察到类似但不太显著的结果。我们的研究结果表明，在SPMS和PPMS的CNS环境，从CSF结果外推确定，可能会刺激内源性池的NPC分化成神经元和少突胶质细胞。(C)2013年IBRO。由爱思唯尔有限公司出版。保留所有权利。
In the adult CNS, tissue-specific germinal niches, such as the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus, contain multipotent neural precursor cells (NPCs) with the capacity to self-renew and differentiate into functional brain cells (Le. neurons, astrocytes or oligodendrocytes). Due to their intrinsic plasticity, NPCs can be considered an essential part of the cellular mechanism(s) by which the CNS tries to repair itself after an injury. In inflammatory CNS disorders, such as multiple sclerosis (MS), neurogenesis and gliogenesis occur as part of an 'intrinsic' self-repair process. However, full and long-lasting repair in progressive MS is not achieved. Recent data suggest that endogenous NPCs, while trying to repair the damaged CNS in MS, may become the target of the disease itself. It is possible that factors produced during MS, like CNS-infiltrating blood-borne inflammatory mononuclear cells, reactive CNS-resident cells, and humoral mediators, can alter the physiological properties of NPCs, ultimately impairing their ability to promote neural regeneration. Here, we investigate the effect of cerebrospinal fluid (CSF) derived from primary progressive (PPMS). and secondary progressive (SPMS) MS patients (CSF MS) on the survival, proliferation, and differentiation of commercially available human embryonic-derived NPCs named ENStem-A. We found that PPMS derived CSF markedly reduced the proliferation of ENStem-A and increased their differentiation toward neuronal and oligodendroglial cells, compared to control CSF. Similar but less striking results were seen when ENstem-A were treated with SPMS derived CSF. Our findings suggest that in both SPMS and PPMS the CNS milieu, as determined by extrapolation from CSF findings, may stimulate the endogenous pool of NPCs to differentiate into neurons and oligodendrocytes. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.