Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Student Research Committee, Social Determinants of Health Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Front Immunol. 2019 Feb 20;10:238. doi: 10.3389/fimmu.2019.00238. eCollection 2019.
Multiple sclerosis (MS) is an inflammatory and degenerative disorder of the central nervous system with unknown etiology. It is accompanied by demyelination of the nerves during immunological processes in the presence of oxidative stress, hypoxia, cerebral hypo-perfusion, and dysregulation in matrix metalloproteinases (MMPs). Human amniotic mesenchymal stem cells (hAMSCs) as pluripotent stem cells possess some conspicuous features which could be of therapeutic value in MS therapy. hAMSCs could mimic the cascade of signals and secrete factors needed for promoting formation of stable neovasculature and angiogenesis. hAMSCs also have immunomodulatory and immunosuppressive effects on inflammatory processes and reduce the activity of inflammatory cells, migration of microglia and inhibit recruitment of certain immune cells to injury sites. hAMSCs attenuate the oxidative stress supported by the increased level of antioxidant enzymes and the decreased level of lipid peroxidation products. Furthermore, hAMSCs enhance neuroprotection and neurogenesis in brain injuries by inhibition of inflammation and promotion of neurogenesis. hAMSCs could significantly increase the expression of neurotrophic factors, which prevents neurons from initiating programmed cell death and improves survival, development, and function of neurons. In addition, they induce differentiation of neural progenitor cells to neurons. hAMSCs could also inhibit MMPs dysregulation and consequently promote the survival of endothelial cells, angiogenesis and the stabilization of vascular networks. Considering the mentioned evidences, we hypothesized here that hAMSCs and their conditioned medium could be of therapeutic value in MS therapy due to their unique properties, including immunomodulation and inflammation suppression; angiogenesis promotion; oxidative stress inhibition; neurogenesis induction and neuroprotection; matrix metalloproteinases regulation; and remyelination stimulation.
多发性硬化症（MS）是一种中枢神经系统的炎症性和退行性疾病，病因不明。它伴随着免疫过程中神经的脱髓鞘，同时存在氧化应激、缺氧、脑低灌注和基质金属蛋白酶（MMPs）失调。人羊膜间充质干细胞（hAMSCs）作为多能干细胞，具有一些显著的特征，在多发性硬化症治疗中可能具有治疗价值。hAMSCs 可以模拟信号级联，并分泌促进稳定新生血管形成和血管生成所需的因子。hAMSCs 还对炎症过程具有免疫调节和免疫抑制作用，降低炎症细胞的活性、小胶质细胞的迁移，并抑制某些免疫细胞向损伤部位的募集。hAMSCs 通过增加抗氧化酶的水平和降低脂质过氧化产物的水平来减轻氧化应激的支持。此外，hAMSCs 通过抑制炎症和促进神经发生来增强脑损伤中的神经保护和神经发生。hAMSCs 可以显著增加神经营养因子的表达，防止神经元启动程序性细胞死亡，并改善神经元的存活、发育和功能。此外，它们诱导神经祖细胞向神经元分化。hAMSCs 还可以抑制 MMPs 失调，从而促进内皮细胞的存活、血管生成和血管网络的稳定。鉴于上述证据，我们假设 hAMSCs 及其条件培养基由于其独特的特性，包括免疫调节和炎症抑制、血管生成促进、氧化应激抑制、神经发生和神经保护、基质金属蛋白酶调节以及髓鞘再生刺激，在多发性硬化症治疗中可能具有治疗价值。
