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This study optimized a protocol to quantify circulating angiogenic cells (CACs), found equivalent CAC levels in women with and without endometriosis, and investigated the role of endometrial stromal cells in angiogenesis, determining they participate in tube formation but do not differentiate into endothelial cells.
Abstract
Endometriosis is a common cause of subfertility and pelvic pain, affecting up to 10% of women of reproductive age. It is characterised by the presence of endometrial-like tissue outside the uterus. The development of the disease is still poorly understood and, currently, the diagnosis relies on visualisation of typical lesions during surgery. There is great interest in identifying biomarkers to assist in diagnosis and disease management. Blood vessel development is known to be a crucial feature of endometriosis, but the mechanisms involved in angiogenesis are not well described for this disease. Most vessel development relies on the proliferation and migration of pre-existing endothelial cells. However, there may also be roles for cells derived from peripheral blood (circulating angiogenic cells) and surrounding stromal cells. In this thesis, the contribution of these different cell types to vessel development in endometriosis is assessed. In chapter 2, a robust protocol was optimised to identify circulating angiogenic cells (CACs) with flow cytometry. The reliability of the protocol was verified, and the level of these cells was found not to fluctuate with the menstrual cycle in healthy women (P=0.279, F=1.359, 3 d.f.). In chapter 3, levels of CACs in women with and without endometriosis were found to be equivalent (0.0835% ± 0.0422 compared to 0.0724% ± 0.0414), demonstrating that they have no use as a disease biomarker. In chapter 4, isolation and culture of endothelial cells from the endometrium was attempted. However, a pure culture of endometrial endothelial cells could not be obtained, which may be due to contamination by other cell types or cellular transdifferentiation. Finally, in chapter 5, the contribution of endometrial stromal cells to vessel development was considered. Stromal cells were found not to differentiate towards an endothelial cell phenotype, but were able to participate in tube formation assays. However, the presence of endometriosis did not influence this behaviour.
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Thesis
Angiogenesis in endometriosis: the role of circulating angiogenic cells and the endometrium
- Abstract:
-
Endometriosis is a common cause of subfertility and pelvic pain, affecting up to 10% of women of reproductive age. It is characterised by the presence of endometrial-like tissue outside the uterus. The development of the disease is still poorly understood and, currently, the diagnosis relies on visualisation of typical lesions during surgery. There is great interest in identifying biomarkers to assist in diagnosis and disease management.
Blood vessel development is known to be a crucial feature of endometriosis, but the mechanisms involved in angiogenesis are not well described for this disease. Most vessel development relies on the proliferation and migration of pre-existing endothelial cells. However, there may also be roles for cells derived from peripheral blood (circulating angiogenic cells) and surrounding stromal cells. In this thesis, the contribution of these different cell types to vessel development in endometriosis is assessed.
In chapter 2, a robust protocol was optimised to identify circulating angiogenic cells (CACs) with flow cytometry. The reliability of the protocol was verified, and the level of these cells was found not to fluctuate with the menstrual cycle in healthy women (P=0.279, F=1.359, 3 d.f.). In chapter 3, levels of CACs in women with and without endometriosis were found to be equivalent (0.0835% ± 0.0422 compared to 0.0724% ± 0.0414), demonstrating that they have no use as a disease biomarker.
In chapter 4, isolation and culture of endothelial cells from the endometrium was attempted. However, a pure culture of endometrial endothelial cells could not be obtained, which may be due to contamination by other cell types or cellular transdifferentiation.
Finally, in chapter 5, the contribution of endometrial stromal cells to vessel development was considered. Stromal cells were found not to differentiate towards an endothelial cell phenotype, but were able to participate in tube formation assays. However, the presence of endometriosis did not influence this behaviour.
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(Preview, pdf, 4.9MB, Terms of use)
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Authors
- Publication date:
- 2012
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
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English
- Keywords:
- Subjects:
- UUID:
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uuid:33c8921c-8320-4559-8298-52d85c8a2987
- Local pid:
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ora:10641
- Deposit date:
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2015-03-19
- ARK identifier:
Terms of use
- Copyright holder:
- Webster, K
- Copyright date:
- 2012
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