Remyelination of chronic demyelinated lesions with directly induced neural stem cells
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The limited ability of CNS progenitor cells to differentiate into oligodendrocytes limits the repair of demyelinating lesions and contributes to the disability of people with progressive multiple sclerosis (PMS). Neural stem cell (NSC) transplantation has emerged as a safe therapeutic approach in people with PMS, where it holds the promise of healing the injured CNS. However, the mechanisms by which NSC grafts could promote CNS remyelination need to be carefully assessed before their widespread clinical adoption.
In this study, we used directly induced NSCs (iNSCs) as a novel transplantation source to boost remyelination in the CNS. Using a mouse model of focal lysophosphatidylcholine (LPC)-induced demyelination, we found that mouse iNSCs promote remyelination by enhancing endogenous oligodendrocyte progenitor cells differentiation and by directly differentiating into mature oligodendrocytes. Transplantation of mouse iNSCs in LPC-lesioned Olig1−/− mice, which exhibits impaired remyelination, confirmed the direct remyelinating ability of grafts and the formation of new exogenous myelin sheaths. We also demonstrated that the xenotransplantation of human iNSCs (hiNSCs) is safe in mice, with hiNSCs persisting long-term in demyelinating lesions where they can produce graft-derived human myelin.
Our findings support the use of NSC therapies to enhance remyelination in chronic demyelinating disorders, such as PMS.
In this study, we used directly induced NSCs (iNSCs) as a novel transplantation source to boost remyelination in the CNS. Using a mouse model of focal lysophosphatidylcholine (LPC)-induced demyelination, we found that mouse iNSCs promote remyelination by enhancing endogenous oligodendrocyte progenitor cells differentiation and by directly differentiating into mature oligodendrocytes. Transplantation of mouse iNSCs in LPC-lesioned Olig1−/− mice, which exhibits impaired remyelination, confirmed the direct remyelinating ability of grafts and the formation of new exogenous myelin sheaths. We also demonstrated that the xenotransplantation of human iNSCs (hiNSCs) is safe in mice, with hiNSCs persisting long-term in demyelinating lesions where they can produce graft-derived human myelin.
Our findings support the use of NSC therapies to enhance remyelination in chronic demyelinating disorders, such as PMS.
Date Issued
2025-07-07
Date Acceptance
2025-05-06
Citation
Brain, 2025, 148 (10), pp.3505-3513
ISSN
0006-8950
Publisher
Oxford University Press (OUP)
Start Page
3505
End Page
3513
Journal / Book Title
Brain
Volume
148
Issue
10
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which per mits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly c
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40622272
PII: 8185601
Subjects
demyelination
iNSC grafts
multiple sclerosis
oligodendrocyte progenitor cells
remyelination
transplantation
Publication Status
Published
Coverage Spatial
England
Article Number
awaf208
Date Publish Online
2025-07-07