Differentiation of human and murine induced pluripotent stem cells to microglia-like cells
Hetal Pandya1, Michael J Shen1, David M Ichikawa1
1National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Microglia are resident inflammatory cells of the CNS and have important roles in development, homeostasis and a variety of neurologic and psychiatric diseases. Difficulties in procuring human microglia have limited their study and hampered the clinical translation of microglia-based treatments shown to be effective in animal disease models. Here we report the differentiation of human induced pluripotent stem cells (iPSC) into microglia-like cells by exposure to defined factors and co-culture with astrocytes. These iPSC-derived microglia have the phenotype, gene expression profile and functional properties of brain-isolated microglia. Murine iPSC-derived microglia generated using a similar protocol have equivalent efficacy to primary brain-isolated microglia in treatment of murine syngeneic intracranial malignant gliomas. The ability to generate human microglia facilitates the further study of this important CNS cell type and raises the possibility of their use in personalized medicine applications.
Insights
Researchers differentiated human induced pluripotent stem cells (iPSC) into microglia. These lab-grown microglia mimic human brain cells, paving the way for new CNS disease treatments and personalized medicine.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Immunology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), are crucial for brain development, homeostasis, and neurological disease pathology.
- Limited availability of human microglia hinders research and the clinical application of microglia-based therapies.
- Existing microglia research heavily relies on animal models, which may not fully translate to human conditions.
Purpose of the Study:
- To develop a reliable method for generating human microglia-like cells from induced pluripotent stem cells (iPSC).
- To characterize the phenotype, gene expression, and functionality of these iPSC-derived microglia.
- To assess the therapeutic potential of iPSC-derived microglia in a preclinical cancer model.
Main Methods:
- Human iPSCs were differentiated into microglia-like cells through exposure to specific growth factors and co-culture with astrocytes.
- Phenotypic, transcriptomic, and functional analyses were performed to compare iPSC-derived microglia with primary human microglia.
- Murine iPSC-derived microglia were tested for efficacy in treating intracranial malignant gliomas in a syngeneic mouse model.
Main Results:
- Successful differentiation of human iPSCs into microglia-like cells with characteristics mirroring primary human microglia.
- iPSC-derived microglia exhibited comparable phenotype, gene expression profiles, and functional properties to their primary counterparts.
- Murine iPSC-derived microglia demonstrated efficacy in treating brain tumors, similar to primary microglia.
Conclusions:
- The generation of human microglia from iPSCs provides a valuable tool for studying CNS diseases and microglia biology.
- This advancement facilitates the investigation of microglia in various neurological and psychiatric conditions.
- iPSC-derived microglia hold promise for future personalized medicine applications in treating CNS disorders.
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