Human-induced pluripotent stem cells: potential for neurodegenerative diseases.
The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using of iPSC models of neurodegenerative disorders, including screening and testing of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics.
Division of Neurobiology, Department of Psychiatry and Departments of Neurology, Neuroscience and Pharmacology, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MA, USA caross@jhu.edu.
Christopher A
CA
Ross
Division of Neurobiology, Department of Psychiatry and.
Sergey S
SS
Akimov
D000544:Alzheimer Disease / Q000235:genetics / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D057180:Frontotemporal Dementia / Q000235:genetics / Q000628:therapy*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000628:therapy*; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D010641:Phenotype