Generating microglia from human pluripotent stem cells: novel in vitro models for the study of neurodegeneration
Anna M Speicher1, Heinz Wiendl1, Sven G Meuth1
1Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
Abstract:
Microglia play an essential role for central nervous system (CNS) development and homeostasis and have been implicated in the onset, progression, and clearance of numerous diseases affecting the CNS. Previous in vitro research on human microglia was restricted to post-mortem brain tissue-derived microglia, with limited availability and lack of scalability. Recently, the first protocols for the generation of microglia from human pluripotent stem cells have become available, thus enabling the implementation of powerful platforms for disease modeling, drug testing, and studies on cell transplantation. Here we give a detailed and comprehensive overview of the protocols available for generating microglia from human pluripotent stem cells, highlighting the advantages, drawbacks, and operability and placing them into the context of current knowledge of human embryonic development. We review novel insights into microglia biology and the role of microglia in neurological diseases as drawn from the new methods and provide an outlook for future lines of research involving human pluripotent stem cell-derived microglia.
Insights
Generating human microglia from pluripotent stem cells offers new avenues for studying neurological diseases. These methods enable scalable research platforms for modeling, drug testing, and cell transplantation in the central nervous system (CNS).
Area of Science:
- Neuroscience
- Stem Cell Biology
- Developmental Biology
Background:
- Microglia are crucial for central nervous system (CNS) development, homeostasis, and disease pathology.
- Previous in vitro studies were limited by the scarcity and scalability of post-mortem human microglia.
- Human pluripotent stem cell (hPSC)-derived microglia represent a significant advancement for research.
Purpose of the Study:
- To provide a comprehensive overview of protocols for generating microglia from hPSCs.
- To highlight the advantages, disadvantages, and practical aspects of these differentiation methods.
- To contextualize these methods within human embryonic development and explore their utility in CNS disease research.
Main Methods:
- Review and synthesis of existing protocols for deriving microglia from human pluripotent stem cells.
- Analysis of the biological characteristics and functional capabilities of hPSC-derived microglia.
- Comparison of different hPSC differentiation strategies and their suitability for various research applications.
Main Results:
- Established protocols enable the generation of microglia with characteristics similar to primary human microglia.
- hPSC-derived microglia offer a scalable and accessible model for studying human microglia biology.
- These models provide novel insights into microglia's role in neurological disease pathogenesis and clearance.
Conclusions:
- Human pluripotent stem cell-derived microglia represent a powerful platform for disease modeling, drug discovery, and cell transplantation studies in the CNS.
- These methods overcome previous limitations in accessing human microglia for research.
- Future research directions include leveraging hPSC-derived microglia to further elucidate microglia biology and neurological disease mechanisms.
More Related Videos
10:53Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions
Published on: November 9, 2020
11:19Human Microglia-like Cells: Differentiation from Induced Pluripotent Stem Cells and In Vitro Live-cell Phagocytosis Assay using Human Synaptosomes
Published on: August 18, 2022
