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1) Neural differentiation of dental pulp stem cells 2) The effect of PDGF, FGF and TGF-β on the proliferation, differentiation and immunomodulatory functions of prospectively-isolated murine mesenchymal stem cells

Suresh, Shankar (2011)
M.Res. thesis, University of Birmingham.

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Abstract 1) A variety of stem/progenitor populations have been isolated from human dental tissue over the past decade. Of these, dental pulp stem cells (DPSCs) are the best characterised. DPSCs reside in a perivascular niche within pulp tissue. Dental pulp originates from cranial neural crest (CNC) cells that migrate and differentiate into a number of cell types, including neurons, during embryonic development. Due to their CNC origin, DPSCs constrictively express certain neural markers, have neurosphere-forming abilities, and have been able to differentiate down the neural lineage in vitro.

In this study, we set out to differentiate rat DPSCs down the neural lineage using a variety of 2D monolayer differentiation protocols originally designed for human DPSCs. Previous studies have indicated that neurosphere formation is a prerequisite for the successful neural induction of rat DPSCs. However, neurosphere formation is labour intensive and is not amenable for robotic scale-up. Our results indicate poor neural induction across all medium formulations tested, as analysed by morphology and immunocytochemistry. Subpopulations of undifferentiated DPSCs expressed early neural markers, but these markers were not upregulated following neural induction. Further work is necessary to optimise the differentiation protocol to work efficiently with rat DPSCs as opposed to human cells.

Abstract 2) Mesenchymal stem cells (MSCs) are a subset of non-haematopoietic, multipotent stem cells found in bone marrow (BM) that are able to differentiate into a variety of lineages. Their plasticity, combined with a potent immunosuppressive ability has led to MSCs being considered as a potential cell source for future therapies. However, progress in elucidating the mechanisms behind the clinical improvements seen in rodent models has been hampered by the heterogeneous populations of MSCs used in most studies, a direct consequence of the plastic-adherence method of MSC isolation.

In this study, we prospectively isolated MSCs (PDGFRα+Sca-1+CD45-TER-119-) from murine BM and examined the effect of PDGF, FGF and TGF-β signalling. Our results showed a marked increase in MSC proliferation in the presence of growth factors (GFs). Addition of PDGF or FGF skewed the differentiation of MSCs towards the adipogenic lineage but reduced their immunosuppressive capabilities. Conversely, TGF-β strongly inhibited both osteogenic and adipogenic differentiation while enhancing their immunomodulatory functions. The findings of this study show that it is possible to ‘prime’ MSCs towards distinct lineages while maintaining their proliferative capacity. This should facilitate research in identifying ‘optimally therapeutic’ populations of MSCs for use in future therapies.

Type of Work:M.Res. thesis.
Supervisor(s):Frampton, Jon and Scheven, Ben and Leadbeater, Wendy and Newsome, Phil
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QR180 Immunology
Institution:University of Birmingham
ID Code:2893
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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