Cited by 381Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsMesenchymal stem cell research

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Dynamics of oligodendrocyte generation in multiple sclerosis

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Yeung, Maggie S. Y., Djelloul, Mehdi, Steiner, Embla, Bernard, Samuel, Salehpour, Mehran, Possnert, Göran, Brundin, Lou, Frisén, Jonas·2019·Nature

DOI 10.1038/s41586-018-0842-3PMC PMC6420067

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Abstract

Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths 1. Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process 2-4. Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans 5-9, it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of 14 C derived from nuclear testing in genomic DNA 10, we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.

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Authors: Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., Brundin, L., & Frisén, J.
Affiliations: Karolinska Institutet (SE)
Lyon 1 Université (FR)
Uppsala University (SE)
Karolinska University Hospital (SE)
Corresponding author: Frisén, Jonas
ORCID: Yeung, Maggie S. Y.
Djelloul, Mehdi
Bernard, Samuel
Salehpour, Mehran
Possnert, Göran
Brundin, Lou
Frisén, Jonas
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-01-23
Volume: 566
Issue: 7745
Pages: 538-542
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-018-0842-3
PMC: PMC6420067
OpenAlex: W2913848851
Cited by: 376
References: 39
Citations by year: 2026: 23 · 2025: 50 · 2024: 50 · 2023: 51 · 2022: 58 · 2021: 53 · 2020: 58 · 2019: 32
FWCI: 36.99
Type: journal article
Language: en
Update notices: correction (2019-02-05)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
HAL (submittedVersion, other-oa)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Cleveland Clinic
Torsten Söderbergs Stiftelse
Swedish Cancer Foundation
Multiple Sclerosis Society (207495)
Knut och Alice Wallenbergs Stiftelse
Vetenskapsrådet
Lerner Research Institute, Cleveland Clinic
Topics: Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: multiple sclerosis, oligodendrocyte generation, remyelination, normal-appearing white matter, demyelinating disease, disease aggressiveness
MeSH terms: Remyelination, Adult, Aging, Cell Differentiation, Cell Separation, Female, Humans, Male, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Case-Control Studies, Age of Onset, Cell Proliferation, White Matter

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