Differentiation of human and murine induced pluripotent stem cells to microglia-like cells
Open accessAbstract
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.
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Protocols have been developed to produce human iPSC-derived microglial-like cells (iMG).
“Recently, protocols for induce human iPSC-derived microglial-like cells (iMG) have been developed [67-71].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [71]
A recently described protocol makes microglia-like cells using astrocyte co-cultures and serum-containing media, with yields comparable to Muffat et al. and amoeboid morphology in vitro and in vivo.
“a protocol described the production of microglia-like cells reliant on astrocyte co-cultures and a serum-based media formulation. This protocol produces cell quantities comparable to Muffat et al., that exhibit amoeboid-like morphology in vitro and in vivo”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Pandya et al., 2017
Pandya et al. (2017) uses FAC sorting/plating on astrocytes/second FAC sorting.
“versus sequential trituration/replating steps for Muffat et al. (2016), fluorescence-activated cell (FAC) sorting/plating on astrocytes/second FAC sorting for Pandya et al. (2017), and low oxygen concentrations/several replatings/five different cytokine cocktails/FAC sorting progenitors for Abud et al. (2017).”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Pandya et al., 2017
Pandya et al. (2017) characterized their iPSC microglia in monoculture following isolation from astrocytes.
“Muffat et al. (2016) characterized their iPSC microglia in monoculture, briefly assessing co-culture, and Pandya et al. (2017) characterized their iPSC microglia in monoculture following isolation from astrocytes.”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Pandya et al., 2017
Our protocol yield is 10-43 per starting iPSC, versus 0.5-4 for Muffat et al. (2016) and Pandya et al. (2017).
“It is robust and efficient: time frame 1 month, versus 2 months for Muffat et al. (2016); yield 10–43 per starting iPSC for our protocol, versus 0.5–4 for Muffat et al. (2016) and Pandya et al. (2017); manipulation consisting of once-weekly feeding of differentiation”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Pandya et al., 2017
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- Authors
- Pandya, H., Shen, M. J., Ichikawa, D. M., Sedlock, A. B., Choi, Y., Johnson, K. R., Kim, G., Brown, M. A., Elkahloun, A. G., Maric, D., Sweeney, C. L., Gossa, S., Malech, H. L., McGavern, D. B., & Park, J. K.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- McGavern, Dorian B
- Park, John K
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-03-02
- Volume
- 20
- Issue
- 5
- Pages
- 753-759
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5404968
- OpenAlex
- W2593638094
- Cited by
- 405
- References
- 41
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 57 · 2023: 28 · 2022: 59 · 2021: 45 · 2020: 56 · 2019: 39 · 2018: 45 · 2017: 25
- FWCI
- 18.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1zians003124-01, ZIA NS003124)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- induced pluripotent stem cells, microglia-like cells, iPSC differentiation, astrocyte co-culture, personalized medicine
- MeSH terms
- Animals, Astrocytes, Cell Differentiation, Cell Movement, Glioma, Humans, Phagocytosis, Survival Analysis, Cytokines, Reactive Oxygen Species, Microglia, Coculture Techniques, Gene Expression Profiling, Xenograft Model Antitumor Assays, Mice, Gene Knock-In Techniques, Induced Pluripotent Stem Cells
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