Stem Cell Reports 2018 11 25;11(5):1199-1210. Epub 2018 Oct 25.
Laboratory of Neuroimmunology, Neuroscience Research Centre, Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland; Service of Neurology, Department of Clinical Neurosciences, CHUV, CHUV BH-10/131, 46, rue du Bugnon, Lausanne 1011, Switzerland. Electronic address:
Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes. Gene expression and functional assays show that our protocol consistently yields a highly enriched population of resting mature astrocytes across the 13 hiPSC lines differentiated. Using this model, we first highlight the importance of serum-free media for astrocyte culture to generate resting astrocytes. Second, we assess the astrocytic response to IL-1β, TNF-α, and IL-6, all cytokines important in neuroinflammation, such as multiple sclerosis. Our study reveals very specific profiles of reactive astrocytes depending on the triggering stimulus. This model provides ideal conditions for in-depth and unbiased characterization of astrocyte reactivity in neuroinflammatory conditions.