Evidence map›Paper›PMID 31729450›Full record

ArticleScientific reports2019

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.

Tanja Hyvärinen, Sanna Hagman, Mervi Ristola, Lassi Sukki, Katariina Veijula, Joose Kreutzer, Pasi Kallio, Susanna Narkilahti

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
–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

112 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Temporal Interference Stimulation Enhances Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Astrocyte Enrichment of 3D Cortical Constructs Enhances Brain Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Silmitasertib, an FDA-designated orphan CK2 inhibitor, ameliorates neuropathology and motor dysfunction in a Huntington's disease mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  13. Review
  14. Mathematical Modeling of Neuroinflammation in Neurodegenerative Diseases.CPT: pharmacometrics & systems pharmacology · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

52 more citing papers are in PubMed but not listed here.

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

8 authors.

Tanja HyvärinenNeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Sanna HagmanNeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.ORCID http://orcid.org/0000-0002-3950-7736
Mervi RistolaNeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Lassi SukkiMicro and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Katariina VeijulaNeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Joose KreutzerMicro and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
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. susanna.narkilahti@tuni.fi.ORCID http://orcid.org/0000-0002-7602-4418

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Cell CommunicationAstrocytesCell DifferentiationCell ProliferationCells, CulturedCell SurvivalCellular MicroenvironmentCoculture TechniquesCytokinesHumansInduced Pluripotent Stem CellsInterleukin-1betaMicrofluidic Analytical TechniquesNeuronsPhenotypePluripotent Stem CellsCytokinesIL1B protein, humanInterleukin-1betaTumor Necrosis Factor-alpha

Identifiers

PMID31729450
PMCPMC6858358

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.