Alzheimer's in a dish - induced pluripotent stem cell-based disease modeling

被引:24
作者
de Leeuw, Sherida [1 ,2 ,3 ]
Tackenberg, Christian [1 ,2 ,3 ]
机构
[1] Univ Zurich, Inst Regenerat Med, Schlieren, Switzerland
[2] Univ Zurich, Neurosci Ctr Zurich, Zurich, Switzerland
[3] Swiss Fed Inst Technol, Zurich, Switzerland
关键词
Alzheimer's disease; Induced pluripotent stem cells; iPSC-derived neurons; iPSC-derived astrocytes; iPSC-derived microglia; Disease modeling; IPSC-DERIVED NEURONS; MICROGLIA-LIKE CELLS; APOLIPOPROTEIN-E; DIRECTED DIFFERENTIATION; DIRECT CONVERSION; HUMAN FIBROBLASTS; AMYLOID-BETA; A-BETA; TAU HYPERPHOSPHORYLATION; FUNCTIONAL-NEURONS;
D O I
10.1186/s40035-019-0161-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Since the discovery of the induced pluripotent stem cell (iPSC) technique more than a decade ago, extensive progress has been made to develop clinically relevant cell culture systems. Alzheimer's disease (AD) is the most common neurodegenerative disease, accounting for approximately two thirds of all cases of dementia. The massively increasing number of affected individuals explains the major interest of research in this disease as well as the strong need for better understanding of disease mechanisms. Main body: IPSC-derived neural cells have been widely used to recapitulating key aspects of AD. In this Review we highlight the progress made in studying AD pathophysiology and address the currently available techniques, such as specific differentiation techniques for AD-relevant cell types as well as 2D and 3D cultures. Finally, we critically discuss the key challenges and future directions of this field and how some of the major limitations of the iPSC technique may be overcome. Conclusion: Stem cell-based disease models have the potential to induce a paradigm shift in biomedical research. In particular, the combination of the iPSC technology with recent advances in gene editing or 3D cell cultures represents a breakthrough for in vitro disease modeling and provides a platform for a better understanding of disease mechanisms in human cells and the discovery of novel therapeutics.
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页数:13
相关论文
共 110 条
[1]   iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases [J].
Abud, Edsel M. ;
Ramirez, Ricardo N. ;
Martinez, Eric S. ;
Healy, Luke M. ;
Nguyen, Cecilia H. H. ;
Newman, Sean A. ;
Yeromin, Andriy V. ;
Scarfone, Vanessa M. ;
Marsh, Samuel E. ;
Fimbres, Cristhian ;
Caraway, Chad A. ;
Fote, Gianna M. ;
Madany, Abdullah M. ;
Agrawal, Anshu ;
Kayed, Rakez ;
Gylys, Karen H. ;
Cahalan, Michael D. ;
Cummings, Brian J. ;
Antel, Jack P. ;
Mortazavi, Ali ;
Carson, Monica J. ;
Poon, Wayne W. ;
Blurton-Jones, Mathew .
NEURON, 2017, 94 (02) :278-+
[2]  
[Anonymous], 2015, BRAIN 11, DOI DOI 10.1093/BRAIN/AWV222
[3]  
[Anonymous], 2014, ADV ALZHEIMERS RES
[4]  
[Anonymous], NEURODEGENERATIVE DI
[5]  
[Anonymous], COLD SPRING HARBOR P
[6]  
[Anonymous], MATTERS
[7]   Tau Biology and Tau-Directed Therapies for Alzheimer's Disease [J].
Bakota, Lidia ;
Brandt, Roland .
DRUGS, 2016, 76 (03) :301-313
[8]  
Bar-Nur O, 2014, NAT METHODS, V11, P1170, DOI [10.1038/NMETH.3142, 10.1038/nmeth.3142]
[9]   MAPT Genetic Variation and Neuronal Maturity Alter Isoform Expression Affecting Axonal Transport in iPSC-Derived Dopamine Neurons [J].
Beevers, Joel E. ;
Lai, Mang Ching ;
Collins, Emma ;
Booth, Heather D. E. ;
Zambon, Federico ;
Parkkinen, Laura ;
Vowles, Jane ;
Cowley, Sally A. ;
Wade-Martins, Richard ;
Caffrey, Tara M. .
STEM CELL REPORTS, 2017, 9 (02) :587-599
[10]   Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer's disease patients [J].
Birnbaum, Julian H. ;
Wanner, Debora ;
Gietl, Anton F. ;
Saake, Antje ;
Kuendig, Thomas M. ;
Hock, Christoph ;
Nitsch, Roger M. ;
Tackenberg, Christian .
STEM CELL RESEARCH, 2018, 27 :121-130