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26 reviewsMetformin rejuvenates adult rat oligodendrocyte progenitor cells (OPCs)allowing more efficient differentiation into oligodendrocytes and improvedremyelination, and therefore is of interest as a therapeutic in demyelinatingdiseases such as multiple sclerosis (MS). Here, we test whether metformin hasa similar effect in human stem cell derived-OPCs. We assess how well humanmonoculture, organoid and chimera model culture systems simulate in vivoadult human oligodendrocytes, finding most close resemblance in the chimeramodel. Metformin increases myelin proteins and/or sheaths in all models evenwhen human cells remain fetal-like. In the chimera model, metformin leads toincreased mitochondrial area both in the human transplanted cells and in themouse axons with associated increase of mitochondrial function/metabolismtranscripts. Human oligodendrocytes from MS brain donors treated premortem with metformin also express similar transcripts. Metformin’s braineffect is thus not cell-specific, alters metabolism in part through mitochondrialchanges and leads to more myelin production. This bodes well for clinical trialstesting metformin for neuroprotection.
