Much interest currently surrounds the emerging field of regenerative medicine. Cell-based therapies represent a novel therapeutic platform for the treatment of ischaemic diseases, shifting the focus clinically from the management of disease symptoms to their potential cure. Endothelial progenitor cells (EPCs) contribute to vascular repair and angiogenesis. Despite controversy surrounding the heterogeneous nature of these cells in vitro and in vivo, their vasoreparative functions suggest that EPCs have potential clinical value. The aim of this thesis is to further define the precise phenotype, angiogenic properties and potential clinical development of two EPC subtypes and to further elucidate the optimal myeloid angiogenic cell (MAC) or outgrowth endothelial cell (OEC) transplant regimen that is safe and effective prior to large-scale clinical application of these cells for therapeutic angiogenesis. EPCs were isolated from human peripheral blood and cord blood by density gradient centrifugation. Mononuclear cells were cultured on fibronectin or collagen and two different isolation protocols were utilised to obtain MACs and OECs respectively. MACs, previously referred to as early EPCs (eEPCs), were found to be M2 alternatively activated macrophages, which induced angiogenesis via release of IL8 in a paracrine manner both in vitro and in vivo. OECs were also assessed in a similar manner, and the effect of high glucose conditions and senescence on their vasoreparative function was evaluated. The effect of cell density on MAC secretome and vascular contribution was also investigated in vitro, as this represents an important Issue in the clinical and commercial development of a cytotherapy This study has provided a complete analysis of both types of EPCs and shed further light on a number of issues associated with the development of a cell-based treatment strategy for autologous or allogeneic therapy. These findings have imp011ant implications in relation to the harnessing of these cells as a cell therapy for vascular repair of ischaemic tissues.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:602718 |
| Date | January 2013 |
| Creators | O'Doherty, Michelle |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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