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Specificities of Living Human Microglial Cells
Giampaolo Milior1, Mariagiovanna Di Chiano2, Melanie Morin-Brureau3
1Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Paris, France. giampaolo.milior@college-de-france.fr.
Advances in Neurobiology
|August 29, 2024
Summary
Rodent models show significant differences from human microglia, impacting brain disorder research. Human ex vivo and in vitro models offer better insights into human microglia function for improved therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's resident macrophages, are crucial for immune surveillance, synaptic remodeling, and neurogenesis.
- Rodent models, particularly mice, are widely used for microglia research due to genetic manipulation accessibility.
- Significant morphological, functional, genetic, and transcriptomic differences exist between human and rodent microglia.
Purpose of the Study:
- To highlight key similarities and differences between human and rodent microglia.
- To re-evaluate the utility of rodent models for human brain disorders.
- To advocate for the use of human ex vivo and in vitro models for studying microglia.
Main Methods:
- Utilizing surgical brain resections (epileptic, tumoral) and post-mortem samples for human microglia studies.
- Generating human-induced pluripotent stem cells (hPSCs) and differentiating them into microglia-like cells.
- Employing human ex vivo and in vitro brain models to mimic in vivo conditions for microglia research.
Main Results:
- Identified significant genetic, transcriptomic, and functional disparities between human and rodent microglia.
- Demonstrated the potential of hPSC-derived microglia for comparative functional studies.
- Highlighted the value of human ex vivo and in vitro models in replicating in vivo human microglia behavior.
Conclusions:
- Rodent microglia models do not fully recapitulate human microglia characteristics, necessitating caution in interpreting results for human brain disorders.
- Human ex vivo and in vitro models provide a more accurate platform for studying human microglia functions.
- Further research using human microglia models can lead to improved understanding and novel therapeutic targets for human brain pathologies.
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