Stem-Cell Challenges in the Treatment of Alzheimer's Disease: A Long Way from Bench to Bedside
Stem-Cell Challenges in the Treatment of Alzheimer's Disease: A Long Way from Bench to Bedside
复制标题
干细胞治疗阿尔茨海默病的挑战：从实验室到临床的漫长道路
DOI：
10.1002/med.21309
复制
发表时间：
2014-09-01
影响因子：
13.3
通讯作者：
Xu, Haiwei
中科院分区：
文献类型：
--
作者：
Fan, Xiaotang;Sun, Dayu;Xu, Haiwei
阿尔茨海默病（AD）是最普遍的痴呆类型，其神经病理学特征在于不溶性β-淀粉样肽的沉积、细胞内神经元缠结和多种神经元的损失。目前AD的药物治疗缓解症状而不影响疾病的主要病理特征。因此，开发新的有效的治疗方法至关重要。干细胞类型包括组织特异性干细胞，例如神经干细胞和间充质干细胞、源自胚泡的胚胎干细胞和从体细胞重编程的诱导多能干细胞（iPSC）。最近的临床前证据表明，干细胞可用于治疗或模拟AD。基于干细胞的治疗AD的机制包括干细胞介导的神经保护和营养作用、抗淀粉样蛋白生成、有益的免疫调节和丢失神经元的替代。iPSC最近已被用于模拟AD，研究散发性和家族性AD发病机制，并筛选抗AD药物。尽管已经取得了相当大的进展，但在将基于干细胞的细胞疗法用于临床AD患者之前，必须克服一系列挑战。本文综述了干细胞治疗AD的最新实验和临床前进展，并讨论了其临床应用的翻译挑战。(C)2014 Wiley Periodicals，Inc.
Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble beta-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuro-protection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application. (C) 2014 Wiley Periodicals, Inc.