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基于祖细胞的胶质疾病治疗。

Progenitor cell-based treatment of glial disease.

作者信息

Goldman Steven A

机构信息

Center for Neuroscience, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, United States.

出版信息

Prog Brain Res. 2017;231:165-189. doi: 10.1016/bs.pbr.2017.02.010. Epub 2017 Apr 13.

Abstract

Diseases of glia, including astrocytes and oligodendrocytes, are among the most prevalent and disabling, yet least appreciated, conditions in neurology. In recent years, it has become clear that besides the overtly glial disorders of oligodendrocyte loss and myelin failure, such as the leukodystrophies and inflammatory demyelinations, a number of neurodegenerative and psychiatric disorders may also be causally linked to glial dysfunction and derive from astrocytic as well as oligodendrocytic pathology. The relative contribution of glial dysfunction to many of these disorders may be so great as to allow their treatment by the delivery of allogeneic glial progenitor cells, the precursors to both astroglia and myelin-producing oligodendrocytes. Given the development of new methods for producing and isolating these cells from pluripotent stem cells, both the myelin disorders and appropriate glial-based neurodegenerative conditions may now be compelling targets for cell-based therapy. As such, glial cell-based therapies may offer potential benefit to a broader range of diseases than ever before contemplated, including disorders such as Huntington's disease and the motor neuron degeneration of amyotrophic lateral sclerosis, which have traditionally been considered neuronal in nature.

摘要

包括星形胶质细胞和少突胶质细胞在内的胶质细胞疾病,是神经学中最常见、最使人丧失能力但却最不为人所重视的病症之一。近年来,已经明确的是,除了明显的少突胶质细胞丢失和髓鞘功能障碍等胶质细胞疾病,如脑白质营养不良和炎性脱髓鞘疾病外,一些神经退行性疾病和精神疾病也可能与胶质细胞功能障碍存在因果关系,并源于星形胶质细胞以及少突胶质细胞的病变。胶质细胞功能障碍对许多此类疾病的相对影响可能非常大,以至于可以通过移植同种异体胶质祖细胞来进行治疗,这些祖细胞是星形胶质细胞和产生髓鞘的少突胶质细胞的前体。鉴于从多能干细胞中产生和分离这些细胞的新方法的发展,髓鞘疾病以及合适的基于胶质细胞的神经退行性疾病现在可能成为基于细胞治疗的有力靶点。因此,基于胶质细胞的疗法可能为比以往任何时候都更广泛的疾病带来潜在益处,包括亨廷顿舞蹈症和肌萎缩侧索硬化症的运动神经元变性等疾病,这些疾病传统上被认为本质上是神经元疾病。

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