title: Differentiation of human and murine induced pluripotent stem cells to microglia-like cells.
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.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hetal
authors.initials: H
authors.lastname: Pandya
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Shen
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ichikawa
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Sedlock
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Choi
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kory R
authors.initials: KR
authors.lastname: Johnson
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Kim
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mason A
authors.initials: MA
authors.lastname: Brown
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Sweeney
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Selamawit
authors.initials: S
authors.lastname: Gossa
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.|Santa Barbara Neuroscience Institute, Santa Barbara, California, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Park
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D055879:Gene Knock-In Techniques; D005910:Glioma / Q000628:therapy; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000502:physiology* / Q000637:transplantation; D010587:Phagocytosis / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species