Nakano Masako, Fujimiya Mineko
Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Neural Regen Res. 2021 Dec;16(12):2359-2366. doi: 10.4103/1673-5374.313026.
Mesenchymal stem cells are multipotent cells that possess anti-inflammatory, anti-apoptotic and immunomodulatory properties. The effects of existing drugs for neurodegenerative disorders such as Alzheimer's disease are limited, thus mesenchymal stem cell therapy has been anticipated as a means of ameliorating neuronal dysfunction. Since mesenchymal stem cells are known to scarcely differentiate into neuronal cells in damaged brain after transplantation, paracrine factors secreted from mesenchymal stem cells have been suggested to exert therapeutic effects. Extracellular vesicles and exosomes are small vesicles released from mesenchymal stem cells that contain various molecules, including proteins, mRNAs and microRNAs. In recent years, administration of exosomes/extracellular vesicles in models of neurological disorders has been shown to improve neuronal dysfunctions, via exosomal transfer into damaged cells. In addition, various microRNAs derived from mesenchymal stem cells that regulate various genes and reduce neuropathological changes in various neurological disorders have been identified. This review summarizes the effects of exosomes/extracellular vesicles and exosomal microRNAs derived from mesenchymal stem cells on models of stroke, subarachnoid and intracerebral hemorrhage, traumatic brain injury, and cognitive impairments, including Alzheimer's disease.
间充质干细胞是具有抗炎、抗凋亡和免疫调节特性的多能细胞。现有治疗神经退行性疾病(如阿尔茨海默病)的药物效果有限,因此间充质干细胞疗法被视为改善神经元功能障碍的一种手段。由于已知间充质干细胞移植后在受损大脑中几乎不会分化为神经元细胞,因此有人提出间充质干细胞分泌的旁分泌因子发挥治疗作用。细胞外囊泡和外泌体是间充质干细胞释放的小囊泡,包含各种分子,包括蛋白质、信使核糖核酸和微小核糖核酸。近年来,在神经疾病模型中给予外泌体/细胞外囊泡已被证明可通过外泌体转移到受损细胞来改善神经元功能障碍。此外,已经鉴定出多种源自间充质干细胞的微小核糖核酸,它们可调节各种基因并减少各种神经疾病中的神经病理变化。本综述总结了间充质干细胞来源的外泌体/细胞外囊泡和外泌体微小核糖核酸对中风、蛛网膜下腔出血和脑出血、创伤性脑损伤以及认知障碍(包括阿尔茨海默病)模型的影响。