Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination.
Experimental autoimmune encephalomyelitis
Human mesenchymal stromal cells
Interleukin 16
Multiple sclerosis
Myelination
Olfactory mucosa
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
29 01 2022
29 01 2022
Historique:
received:
17
01
2022
accepted:
18
01
2022
entrez:
30
1
2022
pubmed:
31
1
2022
medline:
24
3
2022
Statut:
epublish
Résumé
One of the therapeutic approaches for the treatment of the autoimmune demyelinating disease, multiple sclerosis (MS) is bone marrow mesenchymal stromal cell (hBM-MSCs) transplantation. However, given their capacity to enhance myelination in vitro, we hypothesised that human olfactory mucosa-derived MSCs (hOM-MSCs) may possess additional properties suitable for CNS repair. Herein, we have examined the efficacy of hOM-MSCs versus hBM-MSCs using the experimental autoimmune encephalomyelitis (EAE) model. Both MSC types ameliorated disease, if delivered during the initial onset of symptomatic disease. Yet, only hOM-MSCs improved disease outcome if administered during established disease when animals had severe neurological deficits. Histological analysis of spinal cord lesions revealed hOM-MSC transplantation reduced blood-brain barrier disruption and inflammatory cell recruitment and enhanced axonal survival. At early time points post-hOM-MSC treatment, animals had reduced levels of circulating IL-16, which was reflected in both the ability of immune cells to secrete IL-16 and the level of IL-16 in spinal cord inflammatory lesions. Further in vitro investigation revealed an inhibitory role for IL-16 on oligodendrocyte differentiation and myelination. Moreover, the availability of bioactive IL-16 after demyelination was reduced in the presence of hOM-MSCs. Combined, our data suggests that human hOM-MSCs may have therapeutic benefit in the treatment of MS via an IL-16-mediated pathway, especially if administered during active demyelination and inflammation.
Identifiants
pubmed: 35093166
doi: 10.1186/s40478-022-01316-9
pii: 10.1186/s40478-022-01316-9
pmc: PMC8800340
doi:
Substances chimiques
Interleukin-16
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12Subventions
Organisme : Chief Scientist Office
ID : TCS1922
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : TCS/19/22
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0300285
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J004731/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V00381X/1
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZB/4/592
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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