Rae, Peter Colin (2011). The potential role of endothelial progenitor cells for therapeutic angiogenesis. University of Birmingham. Ph.D.
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Rae11PhD.pdf
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Abstract
The natural angiogenic response of the vasculature to cardiovascular disease has been shown, at least in part, to involve circulating endothelial progenitor cells (EPCs). However, the native response is often insufficient to restore vascularity without additional intervention. In this study the angiogenic activity of EPCs, demonstrated by in vitro tubule formation, confirmed the suggested potential of EPCs to be used therapeutically. However, as EPCs are found in limited circulating numbers, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were also investigated as sources of donor EPCs for transplantation. Here ESCs, but not iPSCs, were shown to generate cells with a genetic and proteomic profile, as well as an angiogenic potential, identical to natural EPCs. Using an in vivo mouse model of hindlimb ischemia, this investigation illustrated the preferential binding of transplanted EPCs at sites of angiogenic stimulation, and revealed the importance of platelets in the recruitment of circulating EPCs. In particular, using in vitro aggregation and flow-based adhesion assays, the adhesion molecule P-selectin was shown to play a significant role in this recruitment mechanism. In conclusion, this study has demonstrated that EPC transplantation has abundant potential for development into a viable and efficiacious therapeutic angiogenic treatment.
| Type of Work: | Thesis (Doctorates > Ph.D.) |
|---|---|
| Award Type: | Doctorates > Ph.D. |
| Licence: | |
| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences |
| School or Department: | School of Clinical and Experimental Medicine, Centre for Cardiovascular Sciences |
| Funders: | None/not applicable |
| Subjects: | Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RC Internal medicine R Medicine > RZ Other systems of medicine |
| URI: | http://etheses.bham.ac.uk/id/eprint/3152 |
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