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Title: Investigating the biology of fracture healing : the role of Mesenchymal stem cells, molecular signalling and biological response modifiers
Author: Pountos, Ippokratis
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2011
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Bone healing is a complex event and its outcome is based on the proliferation, differentiation and mineral deposition by Mesenchymal Stem Cells (MSCs). Several cytokines, growth factors and pharmacological agents interfere to variable extent with this process. This thesis is a collection of five studies all analysing the effect of several molecules on the ability of MSCs to proliferate and differentiate. The effect of human serum, BMP-2, BMP-7, PTH and PDGF-BB as well as six antibiotics used commonly in clinical practice on the proliferation and osteogenic differentiation of MSCs was analysed. The previously documented effect of NSAIDs on MSCs' chondrogenesis was further analysed. The results showed that the osteogenic potential of MSCs derived from osteoporotic bone was upregulated with all studied growth factors, but only BMP-7 and PDGF-BB increased proliferation. Autologous serum isolated during the first week after fracture is able to preserve or even enhance the mitogenic and osteogenic potential of MSCs. This effect depends on the time at which serum is extracted and is possibly related to different growth factor content. NSAIDs inhibit the chondrogenic potential of MSCs in-vitro. This effect seems to be linked with the initial chondrogenic differentiation processes and the replenishment of PGE2 levels did not reverse this effect. Antibiotics used parenterally were found to have no effect on the ability of MSCs to proliferate and differentiate towards osteogenic lineage. However, higher plasma concentrations and combinations of different formulations can have a detrimental effect. In conclusion, this study supports the use of BMP-2 and BMP-7 for the enhancement of the healing of osteoporotic bone fractures. If serum is required for exvivo expansion, isolation should take place seven days after surgery. NSAIDs should be considered a risk factor for delayed healing and non-union. Finally, high concentrations or combinations of different antibiotic agents could have a detrimental effect during fracture healing and focussed treatment regimens should be imliated as soon as possible
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available