Multiple Sclerosis Research Center of New York, New York, NY 10019, USA.
Neuroscience. 2013 Oct 10;250:614-21. doi: 10.1016/j.neuroscience.2013.07.022. Epub 2013 Jul 19.
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 (i.e. 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.
在成人中枢神经系统（CNS）中，特定组织的生殖巢，如侧脑室的室下区和海马齿状回的颗粒下区，含有多能神经前体细胞（NPC），具有自我更新和分化为功能性脑细胞（即神经元、星形胶质细胞或少突胶质细胞）的能力。由于其内在的可塑性，NPC 可以被认为是中枢神经系统在受伤后试图自我修复的细胞机制的重要组成部分。在炎症性中枢神经系统疾病（如多发性硬化症（MS））中，神经发生和神经胶质发生是“内在”自我修复过程的一部分。然而，在进行性 MS 中并没有实现完全和持久的修复。最近的数据表明，内源性 NPC 试图修复 MS 中受损的中枢神经系统时，可能成为疾病本身的靶点。在 MS 期间产生的因素，如中枢神经系统浸润的血源性炎症单核细胞、反应性中枢神经系统固有细胞和体液介质，可能改变 NPC 的生理特性，最终损害其促进神经再生的能力。在这里，我们研究了来自原发性进展型（PPMS）和继发性进展型（SPMS）MS 患者的脑脊液（CSF-MS）对商业上可获得的人胚胎源性 NPC 命名为 ENStem-A 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，并增加了其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，也观察到类似但不太明显的结果。我们的研究结果表明，在 SPMS 和 PPMS 中，中枢神经系统环境（通过 CSF 发现推断）可能刺激内源性 NPC 池分化为神经元和少突胶质细胞。
