骨髓间充质干细胞治疗阿尔兹海默病模型小鼠研究进展

Progress in research using mouse models of bone marrow mesenchymal stem cell transplantation for treatment of Alzheimer’s disease

阿尔兹海默病(AD)是一类以认知记忆障碍为主要表现的神经退行性疾病。目前,AD的临床治疗以药物为主,但药物治疗仅能改善症状,不能有效阻止疾病进展,且对中晚期患者疗效欠佳。干细胞具有自我更新和多向分化能力,在AD治疗中有着广阔的应用前景。骨髓间充质干细胞(BM-MSCs)作为最早发现的间充质干细胞,来源方便,易于体外分离、培养、扩增和纯化;具有自我更新及分化为神经样细胞的潜能;其分泌因子具有免疫调控和微环境重塑的能力,因此在AD的临床治疗中有广阔的应用前景。本文综述了国内外BM-MSCs治疗AD的研究现状,主要包括BM-MSCs直接移植,基因修饰后BM-MSCs移植以及BM-MSCs源外泌体移植治疗,深入讨论BM-MSCs治疗阿尔兹海默病模型小鼠的效果、机理及其优缺点,为骨髓间充质干细胞应用于临床提供了数据支撑。

Alzheimer’s disease(AD)is a neurodegenerative disorder characterized by impairment of cognitive memory.The clinical treatment of AD is currently dominated by a few drugs;however,these drugs can only be applied to relieve symptoms without slowing or stopping the progression of AD.Moreover,these drugs have weaker effects in patients with advanced AD.Stem cell therapy is recognized as a promising approach for AD therapy because of the self-renewal and multi-directional differentiation ability of stem cells.As the first described mesenchymal stem cells,bone marrow mesenchymal stem cells(BM-MSCs)are reported to easily expand in the in vitro condition,readily differentiate into neuron-like cells,and contribute to immunomodulation and microenvironment remodeling by producing abundant immunomodulatory molecules.All of these properties endow BM-MSCs a potentially significant role in the clinical treatment of AD.This paper summarizes the current information about the application of BM-MSCs in AD treatment,including direct transplantation of BM-MSCs,transplantation of genetically modified BM-MSCs,and injection of BM-MSC-derived exosomes.The therapeutic effects and underlying mechanisms as well as the advantages and disadvantages of BM-MSCs in AD treatment are also discussed to provide fundamental support for the future clinical application of BM-MSCs.