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Title: Characterisation of the anti-proliferative properties of stromal cells
Author: Jones, Simon
Awarding Body: Imperial College London (University of London)
Current Institution: Imperial College London
Date of Award: 2007
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It has been widely demonstrated that mesenchymal stem cells (MSC) are capable of exerting powerful in vitro and in vivo suppressive effects on virtually all cells of the immune system. However, there is little information as to whether more mature mesenchymal stromal cells (SC) share the same property. To address this, I have characterised mature mesenchymal cells from a variety of tissues including articular cartilage, synovium, skin and lung and cOlTlpared them to MSC. The differentiation potential and surface phenotype of SC was evaluated, whilst the ability of SC from different human tissues to inhibit the proliferation of PBMC following polyclonal stimuli was also 'assessed. Irrespective of their differentiation potential and/or content of progenitor cells, SC from all tissues exhibited anti-proliferative functions. This' was in marked contrast to parenchymal cells from endodermal and ectodermal origins. Although' SC did not interfere with early T lymphocyte activation, they arrested stimulated T cells in the GJGt phase of the cell cycle and rescued them from apoptosis. In addition, IFNy and TNFa production were reduced. I observed that the inhibitory effect is ultimately mediated by soluble factors, the production of which requires SC to be 'licensed' in an inflammatory environment by cell contact. I conclude that the immunosuppressive effect of mesenchymal cells is not confined to multipotent stem cells but is a fundamental characteristic of all stroma. My data suggests that SC, appropriately licensed, regulate T cell homeostasis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available