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

Sylvain Perriot (1) , Amandine Mathias (1) , Guillaume Perriard (1) , Mathieu Canales (1) , Nils Jonkmans (1) , Nicolas Merienne (2) , Cécile Meunier (2) , Lina El Kassar (3) , Anselme Perrier (3) , David-Axel Laplaud (4) , Myriam Schluep (5) , Nicole Déglon (2) , Renaud Du Pasquier (1)

1 CHUV - Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital [Lausanne]
2 Department of Clinical Neurosciences - Laboratory of Neurotherapies and NeuroModulation [Lausanne, Switzerland]
3 I-STEM - Institut des cellules souches pour le traitement et l'étude des maladies monogéniques
4 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity
5 Service of Neurology [CHUV, Lausanne, Switzerland]

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-1b, TNF-a, and IL-6, all cytokines important in neuroinflam-mation, 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: induced pluripotent stem cells; multiple sclerosis; neuroinflammation; differentiation; astrocytes

Domains: Human health and pathology

Sylvain Perriot, Amandine Mathias, Guillaume Perriard, Mathieu Canales, Nils Jonkmans, et al.. Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines. Current Stem Cell Reports, 2018, 11 (5), pp.1199-1210. ⟨10.1016/j.stemcr.2018.09.015⟩. ⟨inserm-02156446⟩