Abstract:
Multiple sclerosis (MS) is an incurable, progressive chronic autoimmune demyelinating disease. Therapy for MS is based on slowing down the processes of neurodegeneration and suppressing the immune system of patients. MS is accompanied by inflammation, axon-degeneration and neurogliosis in the central nervous system. One of the directions for a new effective treatment for MS is cellular, subcellular, as well as gene therapy. We investigated the therapeutic potential of adipose mesenchymal stem cell (ADMSC) derived, cytochalasin B induced artificial microvesicles (MVs) expressing nerve growth factor (NGF) on a mouse model of multiple sclerosis experimental autoimmune encephalomyelitis (EAE). These ADMSC-MVs-NGF were tested using histological, immunocytochemical and molecular genetic methods after being injected into the tail vein of animals on the 14th and 21st days post EAE induction. ADMSC-MVs-NGF contained the target protein inside the cytoplasm. Their injection into the caudal vein led to a significant decrease in neurogliosis at the 14th and 21st days post EAE induction. Artificial ADMSC-MVs-NGF stimulate axon regeneration and can modulate gliosis in the EAE model.
摘要:
多发性硬化症(MS)是一种无法治愈的疾病,进行性慢性自身免疫性脱髓鞘疾病。MS的治疗基于减缓神经变性的过程和抑制患者的免疫系统。MS伴有炎症,中枢神经系统轴突变性和神经胶质增生。一种新的有效治疗MS的方向之一是细胞,亚细胞,以及基因治疗。我们研究了脂肪间充质干细胞(ADMSC)来源的治疗潜力,细胞松弛素B在多发性硬化实验性自身免疫性脑脊髓炎(EAE)的小鼠模型上诱导表达神经生长因子(NGF)的人工微囊泡(MV)。这些ADMSC-MVs-NGF使用组织学测试,在EAE诱导后第14天和第21天注射到动物的尾静脉中后的免疫细胞化学和分子遗传学方法。ADMSC-MVs-NGF在细胞质内含有靶蛋白。在EAE诱导后第14天和第21天,将它们注射到尾静脉导致神经胶质增生的显着减少。在EAE模型中,人工ADMSC-MVs-NGF刺激轴突再生并可调节神经胶质增生。