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Title: The potential of adult human bone marrow - derived cells for repair in Multiple Sclerosis
Author: Mallam, Elizabeth Alison
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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Multiple Sclerosis (MS) is an autoimmune inflammatory disease in which demyelination and neuron degeneration result in neurological disability that remains without cure. Mesenchymal stem cells (MSC) are isolated from adult bone marrow. These multi-potent cells secrete a multitude of factors that have neuroprotective qualities. Practical features make MSC attractive candidates as potential therapy in MS: ease of harvesting, isolation and expansion; potential for long-term bio-preservation; positive safety track-record in the treatment of haematological disorders; immune evasion; and their ability to migrate to areas of damage. In this study bone marrow derived stem cells from patients with MS were characterised according to international criteria. It was demonstrated that, in vitro, these cells bear the same characteristics and proliferation potential as MSC from healthy donors. This gives confidence to the extrapolation of experimental data regarding the potential therapeutic properties of MSC as an autologous treatment in MS. The neuron and axon protective properties of MSC, and possible mechanisms of action, were explored with in vitro experiments. A protective effect against oxidatiye stress was demonstrated. Extracellular secretion of catalase was proposed as a factor contributing to this effect. Intravenous administration of human MSC in an animal model of MS resulted in improved clinical outcomes and a reduction in the amount of demyelination and axonal degeneration. Evidence was found for MSC migration to the cerebellum. CNS migration was more difficult to assess in a focal model of inflammatory demyelinating axonal disease. The area of inflammation and axonal degeneration in the brain was reduced after MSC administration; a benefit that was more significant with syngeneic compared to xenogeneic MSC. Overall these studies add weight to the hypothesis that autologous MSC administration in MS could have beneficial clinical, and pathophysiological, effects, and further exploration of this in the clinical setting should be pursued.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available