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dc.contributor.authorVirani, Sophia
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2011-12-21 19:34:43.054en
dc.date.accessioned2011-12-22T17:58:34Z
dc.date.available2011-12-22T17:58:34Z
dc.date.issued2011-12-22
dc.identifier.urihttp://hdl.handle.net/1974/6920
dc.descriptionThesis (Master, Anatomy & Cell Biology) -- Queen's University, 2011-12-21 19:34:43.054en
dc.description.abstractEndometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Treatment for endometriosis primarily focuses on symptom relief, is short term with severe side effects and often leads to recurrence of the condition. Establishing new blood supply is a fundamental requirement for endometriosis lesions growth. This has led to the idea that antiangiogenic therapy may be a successful approach for inhibiting endometriosis. Recent evidence indicates that endothelial progenitor cells (EPCs) contribute to neoangiogenesis of endometriotic lesions. These EPCs are recruited to the lesion site by stromal cell-derived factor-1 (SDF-1). We hypothesize that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions and that administration of SDF-1 blocking antibody will inhibit lesion growth by inhibiting angiogenesis in a murine model of endometriosis. Immunohistochemistry for SDF-1 and CD34 was performed on human endometriosis and normal endometrial samples. Quantification of SDF-1 and EPCs was performed in the blood of endometriosis patients and controls using ELISA and flow cytometry, respectively. A new mouse model of endometriosis was developed using BALB/c-Rag2-/-/IL2rg-/- mice to investigate role of SDF-1 in neoangiogenesis. Either SDF-1 blocking antibody or an isotype control was administered on a weekly basis for four weeks. Weekly samples of peripheral blood from mice were analyzed for SDF-1, other cytokines of interest and EPCs. Mice were euthanized at seven weeks to observe lesion growth and blood vessel development. Our results indicate overabundance of SDF-1 and CD34+ progenitor cells in human endometriotic lesions compared to eutopic endometrium. In the mouse model, SDF-1 and circulating EPC levels decreased from pre-treatment levels after one week, and remained constant over the course of the treatment in both SDF-1 blocking antibody and isotype control groups. In the SDF-1 blocking group, reduced vascularity of lesions, identified by immunofluorescence staining for CD31, was revealed compared to isotype controls. These findings suggest that SDF-1 may be responsible for CD34+ progenitor cell recruitment to the neoangiogenic sites in endometriosis. Blocking of SDF-1 reduces neovascularization of human endometriotic lesions in a mouse model. Further studies on blocking SDF-1 in combination with other antiangiogenic agents are needed.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectEndothelial progenitor cellsen_US
dc.subjectEPCsen_US
dc.subjectEndometriosisen_US
dc.subjectSndometriumen_US
dc.subjectMouse Model of Endometriosisen_US
dc.subjectStromal Cell-Derived Factor-1en_US
dc.subjectcEPCsen_US
dc.subjectCirculating Endothelial Progenitor Cellsen_US
dc.subjectSDF-1en_US
dc.subjectAngiogenesisen_US
dc.titleRole of Stromal Cell-Derived Factor-1 in Neoangiogenesis in Endometriosis Lesionsen_US
dc.typeThesisen_US
dc.description.degreeMasteren
dc.contributor.supervisorTayade, Chandrakanten
dc.contributor.departmentAnatomy and Cell Biologyen


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