Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination
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...
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BMC
2022-01-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-022-01316-9 |
| _version_ | 1818300235289460736 |
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| author | Susan L. Lindsay Aleksandra M. Molęda Lindsay M. MacLellan Siew Min Keh Daniel E. McElroy Christopher Linington Carl S. Goodyear Susan C. Barnett |
| author_facet | Susan L. Lindsay Aleksandra M. Molęda Lindsay M. MacLellan Siew Min Keh Daniel E. McElroy Christopher Linington Carl S. Goodyear Susan C. Barnett |
| author_sort | Susan L. Lindsay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T05:03:53Z |
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| id | doaj.art-954754aad64c4f218d94ee53a8ea3d31 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-13T05:03:53Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-954754aad64c4f218d94ee53a8ea3d312022-12-21T23:58:42ZengBMCActa Neuropathologica Communications2051-59602022-01-0110112010.1186/s40478-022-01316-9Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelinationSusan L. Lindsay0Aleksandra M. Molęda1Lindsay M. MacLellan2Siew Min Keh3Daniel E. McElroy4Christopher Linington5Carl S. Goodyear6Susan C. Barnett7Institute of Infection, Inflammation and Immunity, University of GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowDepartment of Otolaryngology, Elizabeth University Hospital GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowInstitute of Infection, Inflammation and Immunity, University of GlasgowAbstract 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.https://doi.org/10.1186/s40478-022-01316-9Human mesenchymal stromal cellsOlfactory mucosaMultiple sclerosisExperimental autoimmune encephalomyelitisMyelinationInterleukin 16 |
| spellingShingle | Susan L. Lindsay Aleksandra M. Molęda Lindsay M. MacLellan Siew Min Keh Daniel E. McElroy Christopher Linington Carl S. Goodyear Susan C. Barnett Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination Acta Neuropathologica Communications Human mesenchymal stromal cells Olfactory mucosa Multiple sclerosis Experimental autoimmune encephalomyelitis Myelination Interleukin 16 |
| title | Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination |
| title_full | Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination |
| title_fullStr | Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination |
| title_full_unstemmed | Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination |
| title_short | Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination |
| title_sort | human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for il16 on myelination |
| topic | Human mesenchymal stromal cells Olfactory mucosa Multiple sclerosis Experimental autoimmune encephalomyelitis Myelination Interleukin 16 |
| url | https://doi.org/10.1186/s40478-022-01316-9 |
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