Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell‐Derived Microglia

Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Vol. 37; no. 6; pp. 724 - 730
Main Authors: Haenseler, Walther, Rajendran, Lawrence
Format: Journal Article
Language:English
Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2019
Oxford University Press
Subjects:
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer Disease - therapy
Alzheimer's disease
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - genetics
Amyotrophic Lateral Sclerosis - metabolism
Amyotrophic Lateral Sclerosis - pathology
Amyotrophic Lateral Sclerosis - therapy
Brain
Cell lines
Cell- and Tissue-Based Therapy - methods
Coculture Techniques
Dementia disorders
Disease control
Drug screening
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Experimental models
Frontotemporal dementia
Frontotemporal Dementia - genetics
Frontotemporal Dementia - metabolism
Frontotemporal Dementia - pathology
Frontotemporal Dementia - therapy
Gene Knockout Techniques
Genetic Engineering - methods
Glia
High-Throughput Screening Assays
Humans
Immunology
Induced pluripotent stem cells
Induced Pluripotent Stem Cells - drug effects
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - pathology
Inflammation
Macrophages
Microglia
Microglia - drug effects
Microglia - metabolism
Microglia - pathology
Modelling
Models, Biological
Monoculture
Movement disorders
Myeloid cells
Neurodegeneration
Neurodegenerative diseases
Neuroimmune
Neurological diseases
Neurons - drug effects
Neurons - metabolism
Neurons - pathology
Neuroprotective Agents - therapeutic use
Nootropic Agents - therapeutic use
Parkinson Disease - genetics
Parkinson Disease - metabolism
Parkinson Disease - pathology
Parkinson Disease - therapy
Parkinson's disease
Phenotyping
Pluripotency
Stem cells
Synapses
Yolk sac cell
Myeloid cells
Glia
Yolk sac cell
Induced pluripotent stem cells
Experimental models
Neuroimmune
ISSN:1066-5099, 1549-4918, 1549-4918
Online Access:Get full text
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Summary:Inflammation of the brain and the consequential immunological responses play pivotal roles in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia (FTD). Microglia, the resident macrophage cells of the brain, have also emerged as key players in neuroinflammation. As primary human microglia from living subjects are normally not accessible to researchers, there is a pressing need for an alternative source of authentic human microglia which allows modeling of neurodegeneration in vitro. Several protocols for induced pluripotent stem cell (iPSC)‐derived microglia have recently been developed and provide unlimited access to patient‐derived material. In this present study, we give an overview of iPSC‐derived microglia models in monoculture and coculture systems, their advantages and limitations, and how they have already been used for disease phenotyping. Furthermore, we outline some of the gene engineering tools to generate isogenic controls, the creation of gene knockout iPSC lines, as well as covering reporter cell lines, which could help to elucidate complex cell interaction mechanisms in the microglia/neuron coculture system, for example, microglia‐induced synapse loss. Finally, we deliberate on how said cocultures could aid in personalized drug screening to identify patient‐specific therapies against neurodegeneration. Stem Cells 2019;37:724–730 Modelling of neurological diseases can be done in mono‐cultures for many readouts, but for authentic modelling of neuron‐microglia interactions such as synapse pruning events it is crucial to use co‐cultures.
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.2995