Differentiation of human and murine induced pluripotent stem cells to microglia-like cells
Open Access
- 2 March 2017
- journal article
- research article
- Published by Springer Nature in Nature Neuroscience
- Vol. 20 (5), 753-759
- https://doi.org/10.1038/nn.4534
Abstract
Pandya et al. describe a protocol to differentiate human and mouse iPSCs into cells with the phenotype, transcriptional profile and functional properties of microglia. The treatment of murine intracranial malignant gliomas with these cells demonstrates their potential clinical use. These microglia-like cells will enable further studies into the role of microglia in health and disease. 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.Keywords
This publication has 40 references indexed in Scilit:
- Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cellsNature Neuroscience, 2013
- Transgene-free iPSCs generated from small volume peripheral blood nonmobilized CD34+ cellsBlood, 2013
- Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALSJCI Insight, 2012
- Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantationProceedings of the National Academy of Sciences, 2012
- Nitric Oxide-Mediated Tumoricidal Activity of Murine Microglial CellsTranslational Oncology, 2010
- Macrophage-mediated GDNF Delivery Protects Against Dopaminergic Neurodegeneration: A Therapeutic Strategy for Parkinson's DiseaseMolecular Therapy, 2010
- Induction of glioma apoptosis by microglia-secreted molecules: The role of nitric oxide and cathepsin BBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2009
- ATP mediates rapid microglial response to local brain injury in vivoNature Neuroscience, 2005
- Analysis of Fractalkine Receptor CX3CR1 Function by Targeted Deletion and Green Fluorescent Protein Reporter Gene InsertionMolecular and Cellular Biology, 2000
- Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult miceProceedings of the National Academy of Sciences, 1997