The potential role of endothelial progenitor cells for therapeutic angiogenesis.

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http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/17916 http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/17916 http://eprints.org/relation/isIndexCodesVersionOf http://etheses.bham.ac.uk/id/document/17916 archive 4031 disk0/00/00/31/52 2012-02-02 12:29:58 2019-01-23 09:55:39 2012-02-02 12:29:58 thesis show 0 Rae Peter Colin University of Birmingham The potential role of endothelial progenitor cells for therapeutic angiogenesis. unpub QM QP R1 RC RZ 10col_mede 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into a viable and efficiacious therapeutic angiogenic treatment. 2011-12 2011-08 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties.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. public 336 University of Birmingham School of Clinical and Experimental Medicine, Centre for Cardiovascular Sciences d_ph na 2011-12 graduation