Induced Pluripotent Stem Cell-Derived Astroglia: A New Tool for Research Towards the Treatment of Alzheimer's Disease

被引:4
作者
Atkinson-Dell, Rebecca [1 ]
Mohamet, Lisa [1 ]
机构
[1] StrataStem Ltd, Suite 112,4a Rylands St, Warrington WA1 1EN, Cheshire, England
来源
NEUROGLIA IN NEURODEGENERATIVE DISEASES | 2019年 / 1175卷
关键词
Alzheimer's disease; Induced pluripotent stem cell; Astroglia; Neurodegeneration; Therapeutics; TRANSGENIC MOUSE MODEL; A-BETA; DIRECTED DIFFERENTIATION; ASTROCYTE PATHOLOGY; CEREBRAL ORGANOIDS; BRAIN-DEVELOPMENT; APOLIPOPROTEIN-E; GENERATION; NEURONS; CORTEX;
D O I
10.1007/978-981-13-9913-8_15
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite over a century of research into Alzheimer's disease (AD), progress in understanding the complex aetiology has been hindered, in part, by a lack of human, disease relevant, cellular models, reflected in an inability to translate results from animal studies to successful human therapies. Induced pluripotent stem cell (iPSC) technology, in which somatic cells are reprogrammed to pluripotent stem cells, creates an ideal physiologically relevant model as they maintain the genetic identity of the donor. These iPSCs can self-renew indefinitely in vitro and have the capacity to differentiate into any cell type, opening up new discovery and therapeutic opportunities. Despite a plethora of publications indicating the generation and utility of iPSC-derived neurones for disease modelling to date, in comparison only a limited number of studies have described generation of enriched astroglia from patients with early- or late-stage onset of AD. We recently reported that iPSC-astroglia derived from these patients are capable of mimicking a wide variety of deficits in homeostatic molecular cascades, intimately associated with AD, that are routinely observed in vivo. This review examines the opportunities and limitations of this innovative technology in the context of AD modelling and uses for preclinical discovery to improve our success for an efficacious therapeutic outcome.
引用
收藏
页码:383 / 405
页数:23
相关论文
共 89 条
[1]   MORPHOLOGICAL DIVERSITIES OF CD44 POSITIVE ASTROCYTES IN THE CEREBRAL-CORTEX OF NORMAL SUBJECTS AND PATIENTS WITH ALZHEIMERS-DISEASE [J].
AKIYAMA, H ;
TOOYAMA, I ;
KAWAMATA, T ;
IKEDA, K ;
MCGEER, PL .
BRAIN RESEARCH, 1993, 632 (1-2) :249-259
[2]  
Andriezen WL, 1893, BMJ-BRIT MED J, V2, P227
[3]   Neuronal and Glial Alterations, Increased Anxiety, and Cognitive Impairment Before Hippocampal Amyloid Deposition in PDAPP Mice, Model of Alzheimer's Disease [J].
Beauquis, Juan ;
Vinuesa, Angeles ;
Pomilio, Carlos ;
Pavia, Patricio ;
Galvan, Veronica ;
Saravia, Flavia .
HIPPOCAMPUS, 2014, 24 (03) :257-269
[4]   Environmental enrichment prevents astroglial pathological changes in the hippocampus of APP transgenic mice, model of Alzheimer's disease [J].
Beauquis, Juan ;
Pavia, Patricio ;
Pomilio, Carlos ;
Vinuesa, Angeles ;
Podlutskaya, Natalia ;
Galvan, Veronica ;
Saravia, Flavia .
EXPERIMENTAL NEUROLOGY, 2013, 239 :28-37
[5]   Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia [J].
Berninger, Benedikt ;
Costa, Marcos R. ;
Koch, Ursula ;
Schroeder, Timm ;
Sutor, Bernd ;
Grothe, Benedikt ;
Goetz, Magdalena .
JOURNAL OF NEUROSCIENCE, 2007, 27 (32) :8654-8664
[6]   High Resolution Dissection of Reactive Glial Nets in Alzheimer's Disease [J].
Bouvier, David S. ;
Jones, Emma V. ;
Quesseveur, Gael ;
Davoli, Maria Antonietta ;
Ferreira, Tiago A. ;
Quirion, Remi ;
Mechawar, Naguib ;
Murai, Keith K. .
SCIENTIFIC REPORTS, 2016, 6
[7]   Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy [J].
Bu, Guojun .
NATURE REVIEWS NEUROSCIENCE, 2009, 10 (05) :333-344
[8]   Modeling Development and Disease with Organoids [J].
Clevers, Hans .
CELL, 2016, 165 (07) :1586-1597
[9]   The interlaminar glia: from serendipity to hypothesis [J].
Colombo, Jorge A. .
BRAIN STRUCTURE & FUNCTION, 2017, 222 (03) :1109-1129
[10]  
Cummings Jeffrey, 2018, Alzheimers Dement (N Y), V4, P195, DOI 10.1016/j.trci.2018.03.009