Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination

Autor:	Lindsay, Susan L., Molęda, Aleksandra M., MacLellan, Lindsay M., Keh, Siew Min, McElroy, Daniel E., Linington, Christopher, Goodyear, Carl S., Barnett, Susan C.
Rok vydání:	2022
Předmět:	Interleukin-16 Encephalomyelitis Autoimmune Experimental Experimental autoimmune encephalomyelitis Neurogenesis Research Mesenchymal Stem Cell Transplantation Pathology and Forensic Medicine Multiple sclerosis Cellular and Molecular Neuroscience Mice Myelination Olfactory Mucosa Interleukin 16 Human mesenchymal stromal cells Animals Humans Neurology. Diseases of the nervous system Neurology (clinical) RC346-429 Myelin Sheath
Zdroj:	Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 10, Iss 1, Pp 1-20 (2022)
ISSN:	2051-5960
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa989db7b6d45330714574605d14e54d https://pubmed.ncbi.nlm.nih.gov/35093166 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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