Effects of inflammatory cytokines IFN-γ, TNF-α and IL-6 on the viability and functionality of human pluripotent stem cell-derived neural cells

Sanna Hagman; Aliisa Mäkinen; Laura Ylä-Outinen; Heini Huhtala; Irina Elovaara; Susanna Narkilahti

doi:10.1016/j.jneuroim.2018.07.010

Effects of inflammatory cytokines IFN-γ, TNF-α and IL-6 on the viability and functionality of human pluripotent stem cell-derived neural cells

J Neuroimmunol. 2019 Jun 15:331:36-45. doi: 10.1016/j.jneuroim.2018.07.010. Epub 2018 Aug 29.

Authors

Sanna Hagman¹, Aliisa Mäkinen¹, Laura Ylä-Outinen², Heini Huhtala³, Irina Elovaara⁴, Susanna Narkilahti⁵

Affiliations

¹ Neuroimmunology Unit, Medical School, The Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland; Neuro Group, BioMeditech, The Faculty of Medicine and Life Sciences, University of Tampere, Finland.
² Neuro Group, BioMeditech, The Faculty of Medicine and Life Sciences, University of Tampere, Finland.
³ Faculty of Social Sciences, University of Tampere, Tampere, Finland.
⁴ Neuroimmunology Unit, Medical School, The Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland.
⁵ Neuro Group, BioMeditech, The Faculty of Medicine and Life Sciences, University of Tampere, Finland. Electronic address: susanna.narkilahti@uta.fi.

PMID: 30195439
DOI: 10.1016/j.jneuroim.2018.07.010

Abstract

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease, where neural progenitor cell (NPC) transplantation has been suggested as a potential neuroprotective therapeutic strategy. Since the effect of inflammation on NPCs is poorly known, their effect on the survival and functionality of human NPCs were studied. Treatment with interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ did not induced cytotoxicity, but IFN-γ treatment showed decreased proliferation and neuronal migration. By contrast, increased proliferation and inhibition of electrical activity were detected after TNF-α treatment. Treatments induced secretion of inflammatory factors. Inflammatory cytokines appear to modulate proliferation as well as the cellular and functional properties of human NPCs.

Keywords: Cytokines; Human pluripotent stem cells; IFN-γ; IL-6; Microelectrode array; Multiple sclerosis; Neural cells; TNF-α.

Publication types

Research Support, Non-U.S. Gov't
Video-Audio Media

MeSH terms

Astrocytes / drug effects
Astrocytes / metabolism
Cell Division / drug effects
Cells, Cultured
Cytokines / biosynthesis
Cytokines / genetics
Embryonic Stem Cells / cytology
Gene Expression Regulation / drug effects
Humans
Inflammation
Intercellular Signaling Peptides and Proteins / biosynthesis
Intercellular Signaling Peptides and Proteins / genetics
Interferon-gamma / pharmacology*
Interleukin-6 / pharmacology*
Nerve Net / drug effects
Nerve Tissue Proteins / biosynthesis
Nerve Tissue Proteins / genetics
Neural Stem Cells / drug effects*
Neural Stem Cells / metabolism
Neurogenesis
Neurons / drug effects
Neurons / metabolism
Pluripotent Stem Cells / cytology
Receptors, Cytokine / biosynthesis
Receptors, Cytokine / genetics
Single-Cell Analysis
Time-Lapse Imaging
Tumor Necrosis Factor-alpha / pharmacology*

Substances

Cytokines
Intercellular Signaling Peptides and Proteins
Interleukin-6
Nerve Tissue Proteins
Receptors, Cytokine
Tumor Necrosis Factor-alpha
Interferon-gamma