Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile.
Adv Exp Med Biol. 2019;1147:167-187. doi: 10.1007/978-3-030-16908-4_8.
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease that affects the central nervous system (CNS), particularly, in young adults. Current MS treatments aim to reduce demyelination; however, these have limited efficacy, display side effects and lack of regenerative activities. Oligodendrocyte progenitor cells (OPCs) represents the major source for new myelin. Upon demyelination, OPCs get activated, proliferate, migrate towards the lesion, and differentiate into remyelinating oligodendrocytes. Although myelin repair (remyelination) represents a robust response to myelin damage, during MS, this regenerative phenomenon decays in efficiency or even fails. CNS-resident pericytes (CNS-PCs) are essential for vascular homeostasis regulating blood-brain barrier (BBB) permeability and stability as well as endothelial cells (ECs) function during angiogenesis and neovascularization. Recent studies indicate that CNS-PCs also play a crucial role regulating OPC function during remyelination, and very importantly, these cells are substantially affected in MS. This chapter summarizes important aspects of MS and CNS remyelination as well as it provides new insights supporting the contribution of CNS-PCs to myelin regeneration and to MS pathology. Currently, there is evidence arguing in favor of CNS-PCs as novel therapeutic targets for the development of future treatments for MS.
多发性硬化症 (MS) 是一种影响中枢神经系统 (CNS) 的自身免疫性炎症脱髓鞘疾病,尤其在年轻人中较为常见。目前的 MS 治疗方法旨在减少脱髓鞘,但这些方法疗效有限,存在副作用,且缺乏再生活动。少突胶质前体细胞 (OPC) 是新髓鞘的主要来源。在脱髓鞘后,OPC 被激活、增殖、向病变部位迁移,并分化为髓鞘再生的少突胶质细胞。尽管髓鞘修复(再髓鞘化)是对髓鞘损伤的强烈反应,但在 MS 中,这种再生现象的效率降低,甚至失败。中枢神经系统固有周细胞(CNS-PCs)对于血管稳态至关重要,可调节血脑屏障(BBB)通透性和稳定性,以及血管生成和新生血管形成过程中的内皮细胞(EC)功能。最近的研究表明,CNS-PCs 在调控再髓鞘化过程中的 OPC 功能方面也起着至关重要的作用,非常重要的是,这些细胞在 MS 中受到了极大的影响。本章总结了 MS 和 CNS 再髓鞘化的重要方面,并提供了新的见解,支持 CNS-PCs 对髓鞘再生和 MS 病理学的贡献。目前,有证据表明 CNS-PCs 是开发 MS 治疗新方法的潜在治疗靶点。