Evidence map›Paper›PMID 40542355›Full record

ArticleCell communication and signaling : CCS2025

Modeling neuroinflammatory interactions between microglia and astrocytes in a human iPSC-based coculture platform.

Iisa Tujula, Tanja Hyvärinen, Johanna Lotila, Julia Rogal, Dimitrios Voulgaris, Lassi Sukki, Kaisa Tornberg, Katri Korpela, Henna Jäntti, Tarja Malm and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

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  14. Modulating glutamate neurotransmission inFrontiers in immunology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Iisa Tujula *Neuroimmunology research group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Tanja Hyvärinen *Neuroimmunology research group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Johanna LotilaNeuroimmunology research group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Julia RogalScience for Life Laboratory, Division of Nanobiotechnology, Department of Protein Science, Royal Institute of Technology (KTH), Solna, 171 65, Sweden.
Dimitrios VoulgarisScience for Life Laboratory, Division of Nanobiotechnology, Department of Protein Science, Royal Institute of Technology (KTH), Solna, 171 65, Sweden.
Lassi SukkiMicro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Kaisa TornbergMicro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Katri KorpelaNeuroimmunology research group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Henna JänttiNeuroinflammation research group, Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Tarja MalmNeuroinflammation research group, Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Anna HerlandScience for Life Laboratory, Division of Nanobiotechnology, Department of Protein Science, Royal Institute of Technology (KTH), Solna, 171 65, Sweden.
Pasi KallioMicro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Susanna NarkilahtiNeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Sanna HagmanNeuroimmunology research group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. sanna.hagman@tuni.fi.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMicroglia and astrocytes are central mediators of neuroinflammation in several neurodegenerative diseases. Their intricate crosstalk and contributions to pathogenesis remain elusive, highlighting the need for innovative in vitro approaches for investigating glial interactions in neuroinflammation. This study aimed to develop advanced human-based glial coculture models to explore the inflammatory interactions of microglia and astrocytes in vitro.

methodsHuman induced pluripotent stem cell (iPSC)-derived microglia and astrocytes were cultured both in conventional culture dishes and in a microfluidic coculture platform. This platform features separate compartments for both cell types, enabling the creation of distinct microenvironments with spontaneous migration of microglia toward astrocytes through interconnecting microtunnels. To induce inflammatory activation, glial cultures were stimulated with lipopolysaccharide (LPS), a combination of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), or interferon-γ (IFN-γ) for 24 h. Glial activation and interactions were analyzed with immunocytochemistry, the secretion of inflammatory factors from the culture media was measured, and microglial migration was quantified.

resultsMicroglia-astrocyte cocultures were generated in both conventional cultures and the microfluidic platform. Inflammatory stimulation with LPS and TNF-α/IL-1β elicited cell type-specific responses in microglia and astrocytes, respectively. LPS stimulation of cocultures induced lower secretion of several inflammatory mediators, suggesting dampening of microglial inflammatory responses when cocultured with astrocytes. Notably, inflammatory interaction between glial cells was demonstrated by increased level of IL-10 after TNF-α/IL-1β stimulation in cocultures compared with monocultures. The microfluidic coculture platform enabled the parallel study of microglial migration, glial activation and phagocytic function, thereby facilitating the investigation of glial responses within distinct inflammatory microenvironments. Furthermore, glial inflammatory responses and interactions were demonstrated in the controlled microenvironments of the microfluidic coculture platform. The inflammatory coculture environment was associated with elevated levels of complement component C3, emphasizing the intricate interplay between microglia and astrocytes.

conclusionsOur results depict an elaborate inflammatory interaction between iPSC-derived microglia and astrocytes via reciprocal molecular signaling. Importantly, the microfluidic coculture platform established in this study provides a more functional and advanced setup for investigating inflammatory glial interactions in vitro.

Indexed as

AstrocytesCell CommunicationInduced Pluripotent Stem CellsInflammationMicrogliaModels, BiologicalCell MovementCells, CulturedCoculture TechniquesHumansLipopolysaccharidesTumor Necrosis Factor-alphaLipopolysaccharidesTumor Necrosis Factor-alphaAstrocytesDisease modelingGlial crosstalkiPSCMicrogliaMicrophysiological systemNeuroinflammation

Identifiers

PMID40542355
PMCPMC12181861

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.