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Updated: May 8, 2026
Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research
Published on: September 6, 2024
Development of a culture system to induce microglia-like cells from haematopoietic cells
Daisuke Noto1, Hiroshi Sakuma, Kazuya Takahashi
1Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Aims:
Microglia are the resident immune cells in the central nervous system, originating from haematopoietic-derived myeloid cells. A microglial cell is a double-edged sword, which has both pro-inflammatory and anti-inflammatory functions. Although understanding the role of microglia in pathological conditions has become increasingly important, histopathology has been the only way to investigate microglia in human diseases.
Methods:
To enable the study of microglial cells in vitro, we here establish a culture system to induce microglia-like cells from haematopoietic cells by coculture with astrocytes. The characteristics of microglia-like cells were analysed by flow cytometry and functional assay.
Results:
We show that triggering receptor expressing on myeloid cells-2-expressing microglia-like cells could be induced from lineage negative cells or monocytes by coculture with astrocytes. Microglia-like cells exhibited lower expression of CD45 and MHC class II than macrophages, a characteristic similar to brain microglia. When introduced into brain slice cultures, these microglia-like cells changed their morphology to a ramified shape on the first day of the culture. Moreover, we demonstrated that microglia-like cells could be induced from human monocytes by coculture with astrocytes. Finally, we showed that interleukin 34 was an important factor in the induction of microglia-like cells from haematopoietic cells in addition to cell-cell contact with astrocytes. Purified microglia-like cells were suitable for further culture and functional analyses.
Conclusion:
Development of in vitro induction system for microglia will further promote the study of human microglial cells under pathological conditions as well as aid in the screening of drugs to target microglial cells.
Insights
Researchers developed a new in vitro system to generate microglia-like cells from human monocytes using astrocyte co-culture. This breakthrough facilitates studying these crucial immune cells in neurological diseases and aids drug discovery for microglial targets.
Area of Science:
- Neuroimmunology
- Cell Biology
- Hematopoiesis
Background:
- Microglia are vital resident immune cells in the central nervous system with dual pro- and anti-inflammatory roles.
- Studying human microglia in pathological conditions has been limited, primarily relying on histopathology.
Purpose of the Study:
- To establish a novel in vitro culture system for inducing microglia-like cells from hematopoietic cells.
- To facilitate research into microglial functions in human diseases and drug screening.
Main Methods:
- Induction of microglia-like cells via co-culture of hematopoietic cells (monocytes or lineage-negative cells) with astrocytes.
- Characterization using flow cytometry, functional assays, and morphological analysis in brain slice cultures.
- Identification of key factors, including interleukin 34 and astrocyte cell-cell contact, in the induction process.
Main Results:
- Successfully generated microglia-like cells expressing triggering receptor expressed on myeloid cells-2 from human monocytes and lineage-negative cells.
- These cells displayed reduced CD45 and MHC class II expression compared to macrophages, mimicking brain microglia.
- Induced microglia-like cells adopted a ramified morphology in brain slice cultures and were suitable for further analysis.
Conclusions:
- The developed in vitro induction system enables the study of human microglia outside of histopathological constraints.
- This system will advance research on microglial roles in human diseases and accelerate the screening of drugs targeting microglial cells.
