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


Haenseler, Walther; Rajendran, Lawrence (2019). Concise Review: Modeling Neurodegenerative Diseases with Human Pluripotent Stem Cell-Derived Microglia. Stem Cells, 37(6):724-730.

Abstract

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 mono‐culture 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.

Abstract

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 mono‐culture 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.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Developmental Biology, Molecular Medicine, Cell Biology
Language:English
Date:1 June 2019
Deposited On:23 May 2019 06:37
Last Modified:25 Sep 2019 00:35
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1066-5099
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/stem.2995
Project Information:
  • : FunderSNSF
  • : Grant IDCRSII5_177195
  • : Project TitleMolecular and Cellular Modulation in Parkinson's Disease

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