Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines

Stem Cell Reports. 2018 Nov 13;11(5):1199-1210. doi: 10.1016/j.stemcr.2018.09.015. Epub 2018 Oct 25.


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.

Keywords: astrocytes; differentiation; induced pluripotent stem cells; multiple sclerosis; neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Case-Control Studies
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cytokines / pharmacology*
  • Humans
  • Induced Pluripotent Stem Cells / pathology*
  • Inflammation Mediators / metabolism
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / pathology*
  • Phenotype
  • Remyelination / drug effects
  • Transcriptome / drug effects
  • Transcriptome / genetics


  • Culture Media, Serum-Free
  • Cytokines
  • Inflammation Mediators