Evidence map›Paper›PMID 40885740›Full record

ArticleNature communications2025

Metformin alters mitochondria-related metabolism and enhances human oligodendrocyte function.

Nina-Lydia Kazakou, Nadine Bestard-Cuche, Laura J Wagstaff, Kellie Horan, Luise Seeker, Sunniva Bøstrand, Rana Fetit, Rebecca Sherrard Smith, Fabio Baldivia Pohl, Bjorn Neumann and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Altered Erythrocyte Function via TLR9-ox-mtDNA Binding Links Mitochondrial Oxidative Damage to Systemic Inflammation in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  8. Review
  9. Review
  10. Review
  11. Multiple sclerosis: 2026 update.Free neuropathology · 2026
    Review
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

13 authors.

Nina-Lydia KazakouCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Nadine Bestard-CucheCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Laura J WagstaffCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-3816-6113
Kellie HoranCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0009-0009-1632-5241
Luise SeekerCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Sunniva BøstrandCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Rana FetitCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Rebecca Sherrard SmithCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK.
Fabio Baldivia PohlLaboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-1695-4936
Bjorn NeumannWellcome-MRC Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Patrick KeelerJoint Research Center for Computational Biomedicine, RWTH Aachen University, Aachen, Germany.
Robin J M FranklinWellcome-MRC Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Anna WilliamsCentre for Regenerative Medicine, Institute of Regeneration and Repair, MS Society Edinburgh Centre for MS Research, University of Edinburgh, Edinburgh, UK. anna.williams@ed.ac.uk.ORCID http://orcid.org/0000-0002-6329-382X

Funding

Multiple Sclerosis Society (MS Society) Centre grantRoche (F. Hoffmann-La Roche Ltd) Post doctoral fellowshipWellcome TrustWellcome Trust (Wellcome) Tissue repair PhD studentship
6 · The paper itself

Abstract

Metformin rejuvenates adult rat oligodendrocyte progenitor cells (OPCs) allowing more efficient differentiation into oligodendrocytes and improved remyelination, and therefore is of interest as a therapeutic in demyelinating diseases such as multiple sclerosis (MS). Here, we test whether metformin has a similar effect in human stem cell derived-OPCs. We assess how well human monoculture, organoid and chimera model culture systems simulate in vivo adult human oligodendrocytes, finding most close resemblance in the chimera model. Metformin increases myelin proteins and/or sheaths in all models even when human cells remain fetal-like. In the chimera model, metformin leads to increased mitochondrial area both in the human transplanted cells and in the mouse axons with associated increase of mitochondrial function/metabolism transcripts. Human oligodendrocytes from MS brain donors treated pre-mortem with metformin also express similar transcripts. Metformin's brain effect is thus not cell-specific, alters metabolism in part through mitochondrial changes and leads to more myelin production. This bodes well for clinical trials testing metformin for neuroprotection.

Indexed as

MetforminMitochondriaOligodendrogliaAnimalsAxonsBrainCell DifferentiationCells, CulturedHumansMiceMultiple SclerosisMyelin SheathOligodendrocyte Precursor CellsRatsMetformin

Identifiers

PMID40885740
PMCPMC12398550

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.