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

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

doi:10.1016/j.jneuroim.2018.07.010

Cited by 18 publications

(11 citation statements)

References 50 publications

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“… 6 IFN-γ, TNF-α, and IL-6 also reportedly modulate proliferation as well as both cellular and functional properties of human neural pluripotent cells in vitro. 7 In this study, IL-6 was expressed only in SHED, and IL-3 was 2.77-fold more strongly detected in SHED. Of the core cytokines, SCF and Flt3-L were expressed more strongly in DPSCs and SHED, respectively.…”

Section: Discussionmentioning

confidence: 45%

Distinctive cytokine profiles of stem cells from human exfoliated deciduous teeth and dental pulp stem cells

Kang

Shin

Jeon

et al. 2022

Journal of Dental Sciences

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Background/purpose SHED and DPSC have stem cell regenerative potential, but comparative research on their cytokine profile is rare. This study aimed to investigate and compare cytokine profiles secreted from stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs). Materials and methods SHED-conditioned medium (CM) and DPSC-CM were extracted using seven primary and permanent teeth each. Cytokine membrane array was performed for each CM to quantify and compare the secretomes of 120 cytokines. Enzyme-linked immunosorbent assay, immunocytochemistry, and immunohistochemistry analysis were performed to demonstrate cytokine membrane array analysis. Results Significant differences were observed in the expression levels of 68 cytokines–27 and 41 cytokines were 1.3-fold more strongly expressed in SHED-CM and DPSC-CM, respectively. Cytokines involved in immunomodulation, odontogenesis and osteogenesis were more strongly expressed in SHED-CM. Cytokines involved in angiogenesis were detected more strongly in DPSCs-CM. SHED and DPSCs have distinctive cytokine profiles and characteristics in terms of their stem cell regenerative potential. Conclusion These observations suggest that SHED may have a better cytokine profile related to inflammatory, proliferative, osteogenic, and odontogenic potential.

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Section: Discussionmentioning

confidence: 45%

Distinctive cytokine profiles of stem cells from human exfoliated deciduous teeth and dental pulp stem cells

Kang

Shin

Jeon

et al. 2022

Journal of Dental Sciences

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“…Of note, one EAE study showed that chitinase 3-like-3 (Chi3l3) activates the epidermal growth factor receptor (EGFR) on neural stem cells, which results in decreased disease severity [81]. Moreover, chemokines are important for stem cell proliferation, resulting in a lower capacity to differentiate into oligodendrocytes, and an increased differentiation into neuronal progenitors [77,82]. In contrast, transplanted NSCs were shown to participate directly in the remyelination of damaged axons [83], but also to influence OPC-based myelin regeneration after cuprizone-mediated demyelination [84].…”

Section: Neural Stem Cells (Nscs)mentioning

confidence: 99%

The Molecular Basis for Remyelination Failure in Multiple Sclerosis

Gruchot

Weyers

Göttle

et al. 2019

Cells

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Myelin sheaths in the central nervous system (CNS) insulate axons and thereby allow saltatory nerve conduction, which is a prerequisite for complex brain function. Multiple sclerosis (MS), the most common inflammatory autoimmune disease of the CNS, leads to the destruction of myelin sheaths and the myelin-producing oligodendrocytes, thus leaving behind demyelinated axons prone to injury and degeneration. Clinically, this process manifests itself in significant neurological symptoms and disability. Resident oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) are present in the adult brain, and can differentiate into mature oligodendrocytes which then remyelinate the demyelinated axons. However, for multiple reasons, in MS the regenerative capacity of these cell populations diminishes significantly over time, ultimately leading to neurodegeneration, which currently remains untreatable. In addition, microglial cells, the resident innate immune cells of the CNS, can contribute further to inflammatory and degenerative axonal damage. Here, we review the molecular factors contributing to remyelination failure in MS by inhibiting OPC and NSC differentiation or modulating microglial behavior.

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“…Advancements in the field of stem cell biology have enabled the differentiation of astrocytes from human pluripotent stem cells (hPSCs) 18–22 , providing an unlimited cell source and an option to create disease-specific cell lines. Despite these advancements, only a few studies have described the reactivation of hPSC-derived astrocytes 18,22–25 , and even fewer studies have reported the interplay of inflammation or reactive astrocytes with human neuronal cells 24,26,27 .…”

Section: Introductionmentioning

confidence: 99%

Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system

Hyvärinen

Hagman

Ristola

et al. 2019

Sci Rep

Self Cite

121

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Astrocyte reactivation has been discovered to be an important contributor to several neurological diseases. In vitro models involving human astrocytes have the potential to reveal disease-specific mechanisms of these cells and to advance research on neuropathological conditions. Here, we induced a reactive phenotype in human induced pluripotent stem cell (hiPSC)-derived astrocytes and studied the inflammatory natures and effects of these cells on human neurons. Astrocytes responded to interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) treatment with a typical transition to polygonal morphology and a shift to an inflammatory phenotype characterized by altered gene and protein expression profiles. Astrocyte-secreted factors did not exert neurotoxic effects, whereas they transiently promoted the functional activity of neurons. Importantly, we engineered a novel microfluidic platform designed for investigating interactions between neuronal axons and reactive astrocytes that also enables the implementation of a controlled inflammatory environment. In this platform, selective stimulation of astrocytes resulted in an inflammatory niche that sustained axonal growth, further suggesting that treatment induces a reactive astrocyte phenotype with neurosupportive characteristics. Our findings show that hiPSC-derived astrocytes are suitable for modeling astrogliosis, and the developed in vitro platform provides promising novel tools for studying neuron-astrocyte crosstalk and human brain disease in a dish.

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

Cited by 18 publications

References 50 publications

Distinctive cytokine profiles of stem cells from human exfoliated deciduous teeth and dental pulp stem cells

Distinctive cytokine profiles of stem cells from human exfoliated deciduous teeth and dental pulp stem cells

The Molecular Basis for Remyelination Failure in Multiple Sclerosis

Co-stimulation with IL-1β and TNF-α induces an inflammatory reactive astrocyte phenotype with neurosupportive characteristics in a human pluripotent stem cell model system

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