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The biology of mesenchymal stem cells and the utility of the cellular therapy in Multiple Sclerosis

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Title: The biology of mesenchymal stem cells and the utility of the cellular therapy in Multiple Sclerosis
Authors: Ali, Rehiana
Item Type: Thesis or dissertation
Abstract: Multiple Sclerosis (MS) is the commonest cause of neurological disability in young adults and affects about 100 000 people in the UK. Although there are a number of licensed treatment options there remains an urgent need for neuro-protective and reparative strategies. Mesenchymal stem cells (MSCs) represent a heterogeneous population of cells found in a variety of connective tissue of which bone marrow-derived MSCs (BM-MSCs) are the best characterised. They are multi-potent cells which interact with the adaptive and innate immune system either via direct cell contact or release of soluble factors. The mechanisms to induce peripheral tolerance are well described but varied; the clinical relevance of these, however, is not clear. The Stem cells in Rapidly Evolving Active Multiple Sclerosis (STREAMS) trial was a small phase 2, double-blind randomised controlled cross-over trial of a single intravenous dose of 1-2 x 106 BM-MSCs/kg in MS patients whose objective was to evaluate the safety and efficacy of MSCs. It formed part of a wider collaborative study in MS (MESEMS). 13 patients had successful BM harvests with a mean yield of 3.21 x 106 cells/kg (range 1.66 – 6.78 x 106) but a further six failed to reach the required dose and were withdrawn. There were no significant adverse events in the trial. No significant reduction in the relapse rate, changes in disability measurement or patient reported outcomes was observed. Immunological changes detected ex- vivo included a reduced cell frequency of pathogenic cells such as Th1 and CD1c+ mDCs and an increase was noted in B10 regs post-MSC infusion however the study was under-powered to conclude any significant benefit. There was an increase in the level of TSLP in the CSF which warrants further investigation. Preliminary results from MESEMS confirm safety but failed to demonstrate efficacy of MSCs in reducing enhancing lesions on MRI. Overall, we conclude that MSC therapy appears feasible and safe but no significant evidence exists for clinical therapeutic efficacy.
Content Version: Open Access
Issue Date: Dec-2019
Date Awarded: Oct-2020
URI: http://hdl.handle.net/10044/1/89129
DOI: https://doi.org/10.25560/89129
Copyright Statement: Creative Commons Attribution NonCommercial NoDerivatives Licence
Supervisor: Muraro, Paolo
Sponsor/Funder: Multiple Sclerosis Society of Great Britain and Northern Ireland
UK Stem Cell Foundation
Department: Department of Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses



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