ArticleAnnals of neurology2022
MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes.
Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Neuromodulatory effects of N-acetyl-L-leucine in a human induced neuronal cell culture system.Frontiers in immunology · 2026Article
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- Microglia from patients with multiple sclerosis display a cell-autonomous immune activation state.Journal of neuroinflammation · 2025Article
- From Molecules to Models: miRNAs and Advanced Human Platforms of Neurodegeneration and Repair in Multiple Sclerosis.International journal of molecular sciences · 2025Review
- An inflammation-associated lncRNA induces neuronal damage via mitochondrial dysfunction.Molecular therapy. Nucleic acids · 2025Article
- Human-based complexFrontiers in cell and developmental biology · 2025Review
- Novel human iPSC models of neuroinflammation in neurodegenerative disease and regenerative medicine.Trends in immunology · 2024Review
- A glia-enriched stem cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis.Cell reports. Medicine · 2024Article
- Orchestrating Stress Responses in Multiple Sclerosis: A Role for Astrocytic IFNγ Signaling.International journal of molecular sciences · 2024Review
- Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient.International journal of molecular sciences · 2024Article
- Brain organoid methodologies to explore mechanisms of disease in progressive multiple sclerosis.Frontiers in cellular neuroscience · 2024Review
- Research progress of autoimmune diseases based on induced pluripotent stem cells.Frontiers in immunology · 2024Review
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAstrocytes play a significant role in the pathology of multiple sclerosis (MS). Nevertheless, for ethical reasons, most studies in these cells were performed using the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism.
methodsWe obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls, and performed electron microscopy, flow cytometry, cytokine and glutamate measurements, gene expression, in situ respiration, and metabolomics. We validated our findings using a single-nuclei RNA sequencing dataset.
resultsWe detected several differences in MS astrocytes including: (i) enrichment of genes associated with neurodegeneration, (ii) increased mitochondrial fission, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) impaired uptake and enhanced release of glutamate, (v) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (vi) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS.
interpretationHere we describe the metabolic profile of iPSC-derived astrocytes from PwMS and validate this model as a very powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies. ANN NEUROL 2022;91:652-669.
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