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

Lindsay, S. L. , Molęda, A. M., MacLellan, L. M., Keh, S. M., McElroy, D. E., Linington, C. , Goodyear, C. S. and Barnett, S. C. (2022) Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination. Acta Neuropathologica Communications, 10, 12. (doi: 10.1186/s40478-022-01316-9) (PMID:35093166) (PMCID:PMC8800340)

Abstract

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.

• Item Type: Articles
• Additional Information: The authors gratefully acknowledge the funding from the Chief Scientist Office (Grant number: TCS1922/CSO), the Multiple Sclerosis Society (Grant number: 056/MSS) and the Medical Research Council (Grant number: MR/V00381X/1/MRC).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Barnett, Professor Susan and Lindsay, Dr Susan and Linington, Professor Christopher and McElroy, Dr Daniel and Keh, Miss Siew and Maclellan, Dr Lindsay and Goodyear, Professor Carl
• Authors: Lindsay, S. L., Molęda, A. M., MacLellan, L. M., Keh, S. M., McElroy, D. E., Linington, C., Goodyear, C. S., and Barnett, S. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Acta Neuropathologica Communications
• Publisher: BioMed Central
• ISSN: 2051-5960
• ISSN (Online): 2051-5960
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Acta Neuropathologica Communications 10: 12
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
309989		Heparin mimetics: Novel non-anticoagulant compounds to promote CNS repair	Susan Barnett	Medical Research Council (MRC)	MR/V00381X/1	III - Immunology