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Updated: Apr 29, 2026
Author Spotlight: Induced Microglia-Like Cell Technology to Shed Light on the Role of Microglial Dysfunction in Neuropsychiatric Disorders
Published on: September 6, 2024
Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu-Hakola
Masahiro Ohgidani1, Takahiro A Kato2, Daiki Setoyama3
1Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Abstract:
Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders.
Insights
Researchers developed induced microglia-like (iMG) cells from human blood to study brain disorders. These iMG cells mimic human microglia, offering new insights into neurological and psychiatric conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglia are crucial in neurological and psychiatric disorders, but their in vivo function in the human brain remains unclear.
- Current research relies heavily on rodent models and postmortem human studies, limiting understanding of dynamic microglial behavior.
Purpose of the Study:
- To develop a novel technique for generating induced microglia-like (iMG) cells from human peripheral blood.
- To characterize the functional properties of these iMG cells.
- To explore the clinical utility of iMG cells in studying microglial dysfunction in diseases like Nasu-Hakola disease (NHD).
Main Methods:
- Human peripheral blood monocytes were differentiated into iMG cells using an optimized cocktail of cytokines (GM-CSF and IL-34) over 14 days.
- Characterization of iMG cells included marker expression, morphology assessment, phagocytic activity, and cytokine release profiling.
- iMG cells were generated from a patient with Nasu-Hakola disease (NHD) for comparative analysis with healthy controls.
Main Results:
- The developed iMG cells exhibited key microglial characteristics, including specific marker expression, ramified morphology, phagocytic capacity, and cytokine secretion.
- iMG cells derived from an NHD patient showed distinct inflammatory responses, characterized by delayed but heightened inflammatory reactions compared to healthy controls.
- This demonstrates the potential of iMG cells to model disease-specific microglial dysfunction.
Conclusions:
- The novel iMG cell generation technique provides a valuable in vitro model for studying human microglia.
- This approach facilitates the investigation of microglial roles in various brain disorders, overcoming limitations of previous study methods.
- iMG cells hold promise for elucidating unresolved aspects of human microglia function and dysfunction in neurological and psychiatric diseases.
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