Sekiya, T. orcid.org/0000-0002-1325-5331 and Holley, M.C. (2025) The glial scar: to penetrate or not for motor pathway restoration? Cell Transplantation, 34. ISSN 0963-6897
Abstract
Although notable progress has been made, restoring motor function from the brain to the muscles continues to be a substantial clinical challenge in motor neuron diseases/disorders such as spinal cord injury (SCI). While cell transplantation has been widely explored as a potential therapeutic method for reconstructing functional motor pathways, there remains considerable opportunity for enhancing its therapeutic effectiveness. We reviewed studies on motor pathway regeneration to identify molecular and ultrastructural cues that could enhance the efficacy of cell transplantation. While the glial scar is often cited as an intractable barrier to axon regeneration, this mainly applies to axons trying to penetrate its “core” to reach the opposite side. However, the glial scar exhibits a “duality,” with an anti-regenerative core and a pro-regenerative “surface.” This surface permissiveness is attributed to pro-regenerative molecules, such as laminin in the basement membrane (BM). Transplanting donor cells onto the BM, which forms plastically after injury, may significantly enhance the efficacy of cell transplantation. Specifically, forming detour pathways between transplanted cells and endogenous propriospinal neurons on the pro-regenerative BM may efficiently bypass the intractable scar core and promote motor pathway regeneration. We believe harnessing the tissue’s innate repair capacity is crucial, and targeting post-injury plasticity in astrocytes and Schwann cells, especially those associated with the BM that has predominantly been overlooked in the field of SCI research, can advance motor system restoration to a new stage. A shift in cell delivery routes—from the traditional intra-parenchymal (InP) route to the transplantation of donor cells onto the pro-regenerative BM via the extra-parenchymal (ExP) route—may signify a transformative step forward in neuro-regeneration research. Practically, however, the complementary use of both InP and ExP methods may offer the most substantial benefit for restoring motor pathways. We aim for this review to deepen the understanding of cell transplantation and provide a framework for evaluating the efficacy of this therapeutic modality in comparison to others.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
Keywords: | axon regeneration; basement membrane; cell delivery; corticospinal tract; glial scar |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Apr 2025 13:45 |
Last Modified: | 08 Apr 2025 13:45 |
Status: | Published |
Publisher: | SAGE Publications |
Refereed: | Yes |
Identification Number: | 10.1177/09636897251315271 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:225296 |
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