A Model of mammary microvasculature: evaluating hormone responsiveness and luminal-like tumor integration
This thesis aims to fill gaps in the research on breast microvasculature by creating a perfusable microvasculature system within a microfluidic platform. For the first time, we co-cultured primary breast endothelial cells and fibroblasts to establish mammary-specific microvessels. Using this system,...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/694422 |
| Acceso en línea: | http://hdl.handle.net/10803/694422 |
| Access Level: | acceso abierto |
| Palabra clave: | Mammary gland Microvasculature Sex hormones Breast cancer Microfluidic technology Glándula mamaria Microvasculatura Hormonas sexuales Cáncer de mama Tecnología microfluídica 576 |
| Sumario: | This thesis aims to fill gaps in the research on breast microvasculature by creating a perfusable microvasculature system within a microfluidic platform. For the first time, we co-cultured primary breast endothelial cells and fibroblasts to establish mammary-specific microvessels. Using this system, the two main aims are to explore dose-dependent responses of breast microvasculature to sex hormones and integrate luminal-like breast cancer. To achieve the first objective, we simulate different phases of the menstrual cycle by combining varying concentrations of estrogen and progesterone. The evaluation encompasses vascular remodeling, barrier function, and the release of angiogenic factors within the mammary microvasculature. Tissue specificity is ensured by comparing the breast-specific microvasculature with an alternative model using endothelial cells from a different source and breast fibroblasts. In the second aim, a mammary epithelial layer is integrated, mimicking a lactiferous duct. This setup enables us to investigate the barrier properties of the mammary duct, including the influence of hormonal fluctuations and the effects of tamoxifen. Ultimately, luminal-like breast cancer is incorporated into the system alongside the epithelial mammary layer, simulating ductal carcinoma. This addition contributes to a distinctive 3D model and enhances our comprehension of drug delivery dynamics. |
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