Differentiation of human and murine induced pluripotent stem cells to microglia-like cells

Abstract

Microglia are the resident inflammatory cells of the central nervous system (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 (iPS-MG) have the phenotype, gene expression profile and functional properties of brain-isolated microglia. Murine iPS-MG generated using a similar protocol have equivalent efficacy to primary brain-isolated microglia in the 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.

iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases

“…More recently, 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 (Pandya et al, 2017). Thus, some questions remain in terms of yield, scalability, and purity of homeostatic microglia using these other methods and whether the resulting cells can be used to interrogate microglial function in quantitative assays that require large numbers of pure microglia-like cells.…”

Directed Differentiation of Human Pluripotent Stem Cells to Microglia

“…(2017). In contrast, mRNA was not considered expressed in human primary microglia (Muffat et al., 2016 and our study) or iPSC-derived microglia (Muffat et al., 2016) and varied in our iPSC-MG. Transcript levels of CX3CR1 were also relatively low and variable in the Pandya et al. (2017) study despite detectable protein expression by FACS.…”

An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells

“…Our hiPSC-astrocytes overcome these drawbacks, making possible hiPSC-based astrocyte-neuron (Jiang et al., 2013) and astrocyte-microglia (Muffat et al., 2016, Pandya et al., 2017) co-culture platforms for uncovering disease-related mechanisms in vitro , which should help to reveal how the crosstalk between these three neural cell types contributes to neurological and psychiatric disease.…”