Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis
Open accessAbstract
The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that MSC isolated from patients with progressive MS (MS-MSC) have reduced expansion potential, premature senescence, and reduced neuroprotective potential in vitro. In view of the role of antioxidants in ageing and neuroprotection, we examined the antioxidant capacity of MS-MSC demonstrating that MS-MSC secretion of antioxidants superoxide dismutase 1 (SOD1) and glutathione S-transferase P (GSTP) is reduced and correlates negatively with the duration of progressive phase of MS. We confirmed reduced expression of SOD1 and GSTP by MS-MSC along with reduced activity of SOD and GST and, to examine the antioxidant capacity of MS-MSC under conditions of nitrosative stress, we established an in vitro cell survival assay using nitric oxide-induced cell death. MS-MSC displayed differential susceptibility to nitrosative stress with accelerated senescence and greater decline in expression of SOD1 and GSTP in keeping with reduced expression of master regulators of antioxidant responses nuclear factor erythroid 2-related factor 2 and peroxisome proliferator-activated receptor gamma coactivator 1-α. Our results are compatible with dysregulation of antioxidant responses in MS-MSC and have significant implications for development of autologous MSC-based therapies for MS, optimization of which may require that these functional deficits are reversed. Furthermore, improved understanding of the underlying mechanisms may yield novel insights into MS pathophysiology and biomarker identification.
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A reduction in GSH and the GSH/GSSG ratio is often reported during normal aging and in cellular senescence.
“a reduction in GSH and the GSH/GSSG ratio are often reported during normal aging and in cellular senescence, both conditions influenced by OS [183,184,185,186].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [185]
Normal aging and cellular senescence are conditions influenced by oxidative stress.
“both conditions influenced by OS [183,184,185,186].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [185]
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A Preview of Selected Articles
Atkinson, S. P. (2017) · Stem Cells Translational Medicine · doi:10.1002/sctm.17-0254
A Preview of Selected Articles
Atkinson, S. P. (2018) · Stem Cells Translational Medicine · doi:10.1002/sctm.18-0194
Ahmed, A. A., Fayez, S., Rashed, L. A., Ragab, N., Mohamed, R. S., & Mohamed, D. M. G. (2024) · Reports of Biochemistry and Molecular Biology · doi:10.61186/rbmb.12.4.512
- Authors
- Redondo, J., Sarkar, P., Kemp, K., Heesom, K. J., Wilkins, A., Scolding, N. J., & Rice, C. M.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Rice, Claire M
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-07-31
- Volume
- 7
- Issue
- 10
- Pages
- 748-758
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- PMC
- PMC6186266
- OpenAlex
- W2886181399
- Cited by
- 37
- References
- 58
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 2
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cells Translational Medicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- Explore Bristol Research (publishedVersion, cc-by)
- Funders
- Burden Neurological Institute
- Friends of Frenchay
- Catholic Bishops of England and Wales
- Rosetree's Trust
- Multiple Sclerosis Trust
- The Silverman Family Foundation
- Medical Research Council (MR/K004166/1)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- mesenchymal stem cells, progressive multiple sclerosis, antioxidant response, superoxide dismutase 1, glutathione S-transferase pi, nitrosative stress, cellular senescence, Nrf2, PGC-1α, autologous cell therapy, neuroprotection, disease duration
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Superoxide Dismutase-1, Antioxidants, Bone Marrow Cells, Female, Glutathione Transferase, Humans, Male, Middle Aged, Multiple Sclerosis, Nitroso Compounds, Cellular Senescence, Mesenchymal Stem Cell Transplantation, NF-E2-Related Factor 2, Mesenchymal Stem Cells
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