Laboratory of Neurobiology, Department of Neurology, Institute of Neurosciences, San Carlos Health Research Institute, Universidad Complutense, 28040 Madrid, Spain.
Department of Physiology, Ciudad Real School of Medicine, Universidad de Castilla-La Mancha, 13001 Ciudad Real, Spain.
Int J Mol Sci. 2021 May 14;22(10):5192. doi: 10.3390/ijms22105192.
AQP4 (aquaporin-4)-immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4-IgG in cell differentiation.
We included three groups-a group of patients with AQP4-IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines.
The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.
水通道蛋白 4(AQP4)-免疫球蛋白 G(IgG)介导的视神经脊髓炎谱系疾病(NMOSD)是一种影响中枢神经系统的炎症性脱髓鞘疾病,特别是脊髓和视神经;视神经脊髓炎的髓鞘再生能力尚未确定,AQP4-IgG 在细胞分化中的作用也尚未确定。
我们纳入了三组患者-一组 AQP4-IgG 阳性的视神经脊髓炎患者,一组健康对照组,一组假手术组。我们通过在早期和晚期分化两个不同时间点添加血清来分析来自小鼠侧脑室下区的神经球的分化能力。我们还分析了向不同细胞系的分化。
NMOSD 患者血清对前体细胞的影响因分化程度而异,可能对从 NG2 细胞到少突胶质前体细胞的少突胶质祖细胞的影响较小,但由此产生的少突胶质细胞在成熟方面可能存在缺陷,并且可能限制其产生髓鞘的能力。此外,这些细胞随年龄增长而减少。在视神经脊髓炎的情况下,使用有利于多发性硬化症中少突胶质前体细胞迁移和分化的药物不太可能有效,但使用少突胶质前体细胞的细胞治疗似乎是一种潜在的替代方法。