Severe experimental autoimmune encephalomyelitis (EAE) is ameliorated by human olfactory-derived mesenchymal stromal cell transplantation

Lindsay, S.L. , McElroy, D.E., Goodyear, C.S. and Barnett, S.C. (2017) Severe experimental autoimmune encephalomyelitis (EAE) is ameliorated by human olfactory-derived mesenchymal stromal cell transplantation. XIII European Meeting on Glial Cells in Health and Disease, Edinburgh, Scotland, 08-11 Jul 2017. E516. (doi: 10.1002/glia.23157)

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Abstract

Currently, bone marrow-derived mesenchymal stromal cells (BM-MSCs) are being tested in the clinic for the treatment of the demyelinating disease, Multiple Sclerosis (MS). Their immunomodulatory action, which targets the inflammatory component of the disease, is thought to make them ideal candidates. However, a treatment which suppresses disease activity whilst also promoting endogenous remyelination would be considered to be advantageous. We have identified a novel MSC type from the human olfactory mucosa (OM-MSCs), which we have shown to enhance CNS myelination in vitro to a greater extent than those derived from bone marrow. In addition, we have demonstrated that OM-MSCs secrete less of the pro-inflammatory chemokines, IL-6, IL-8 and CCL2 than BM-MSCs and skew microglia to an anti-inflammatory phenotype. We, therefore, postulated that OM-MSCs may have therapeutic benefits over BM-MSCs in the treatment of MS, as a result of their secreted chemokine milieu and their enhanced myelinating capabilities. In this investigation, we have compared the reparative properties of OM-MSCs to BM-MSCs using the animal model of MS, experimental autoimmune encephalomyelitis (EAE). We have shown that both MSC types are capable of ameliorating the disease compared to PBS control injected animals, if cells are delivered intravenously (1 x 106 cells) at early disease i.e. when animals achieve a score of 1 on the EAE score (loss of tail tone). However, when administered during established severe disease (score of 3 or above; hindlimb paralysis), only OM-MSCs significantly improved disease outcome. Furthermore, histological examination revealed an increased number of remyelinated axons, and a reduction in the inflammatory infiltrate after treatment with OM-MSCs compared to BM-MSCs or PBS control injected animals. This research has shown that OM-MSCs may have therapeutic benefits over BM-MSCs in the treatment of demyelinating conditions, such as MS, especially if administered during progressive disease. Thus OM-MSCs could be a better cell choice for use in the clinic.

Item Type:Conference or Workshop Item
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McElroy, Dr Daniel and Barnett, Professor Susan and Lindsay, Dr Susan and Goodyear, Professor Carl
Authors: Lindsay, S.L., McElroy, D.E., Goodyear, C.S., and Barnett, S.C.
Subjects:Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Group:Barnett Lab
ISSN:0894-1491
Published Online:12 June 2017

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172239Are mesenchymal stem cells (MSCs) isolated from the olfactory mucosa a better source of cells for treatment of MS than bone marrow MSCsSusan BarnettNational Multiple Sclerosis Society (NATMSSOC)RG-1501-02703III - Immunology