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Title: Recognition and manipulation of adult stem cells through haematopoietic and non-haematopoietic differentiation pathways for intended therapeutic clinical applications
Author: Tura-Ceide, Olga
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Studies are presented which focus on autologous stem cells for autograft cellular therapies in (1) improvement of early haematopoietic reconstitution by ex vivo manipulation of graft cells, and (2) assessment of the angiogenic potential of available clinical sources for development of therapies for vascular regeneration in ischaemic tissue. There remains a period following HSC autograft when patients are neutropenic and thrombocytopenic. A number of studies have attempted simultaneous ex vivo expansion of progenitors of neutrophil and megakaryocyte lineages to reduce post transplant neutropenia and thrombocytopenia. Our results show that CD34+ HSCs could expand into mature functional neutrophils under the influence of SCF + Flt3-L + G-CSF, but that the addition of other cytokines did not improve CD34+ expansion, and the megakaryocytic growth factor TPO reduced neutrophil maturation. Endothelial progenitor cells (EPCs) are stem cells with the potential to proliferate and differentiate into mature endothelial cells and to form blood vessels in a process resembling embryonic vasculogenesis. Autologous EPC transplantation may be used to promote endothelial reconstitution in patients with ischaemic or infracted tissue. EPC appear to share many properties with HSC, but while haematopoietic potential is now assessed by numbers of HSC expressing CD34, EPC determination remains ambiguous. Bone marrow and mobilised peripheral blood are HSC-rich sources which have been used for vasculogenic therapy. The studies presented here show that there is no correlation between the diverse EPC phenotype definitions proposed in the literature. There is no obvious relationship between the numbers of haematopoiesis related CD34+ or CD133+ cells and outcome of the EPC-CFU assay. The cells responsible for these early outgrown EPC-CFU colonies were CD14+ colonies were CD14+ plastic-adherent monocyte-like cells. Recent reports indicate that a peripheral blood myelocyte monocytes population may also be considered as an EPC source with potential angiogenic clinical capability. Further work is required to better define the relative endothelial potential of these sources for development of clinical autograft vascular regenerative therapies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available