Engineering an in vitro model of the mammary gland

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The breast (mammary gland) is a complex, highly specialised tissue that has evolved to provide nutrition for the young. This essential life-giving role for the breast does not come without cost to the mother as this tissue is highly susceptible to cancer, with breast cancer being one of the most likely forms of death for women. The human breast is unusual amongst adult organs in that it undergoes dramatic, and cyclical, changes during the lifetime of a female animal. With each successive pregnancy, the cells of the mammary gland undergo cycles of proliferation, differentiation, secretion and programmed cell death. It is estimated that the number of epithelial cells increases by approximately 100-fold during pregnancy in response to hormones and other secreted factors. Our current knowledge of the processes involved in these complex changes in cell composition and function have been derived from the use of experimental animals, mainly mice. It is possible to genetically modify mice such that they 'lose' the function of a particular gene thereby allowing the role of this gene in breast development to be defined and studied at the molecular level. The mouse has been used extensively also for studies on tumour development, and is used as a model for breast cancer. The aim of this project is to engineer a model of the mammary gland that can be grown in culture so that the use of rodents can be dramatically reduced. If this project is successful, we will also develop a human version of this model so that studies can be carried out in the most relevant tissue for human disease. This is particularly important when testing new therapeutic drugs that may have undesired side effects or may work differently in rodents compared to humans. This project will combine the skills of two departments in Cambridge: the Department of Materials Science and Metallurgy and the Department of Pathology. This will bring together expertise in tissue engineering and in breast biology. The aim is to build a polymer scaffold in which both fat cells and breast epithelial cells can be grown and subsequently treated with a variety of reagents to induce growth and branching. Once formed, the mammopad can be treated with agents that induce or knockdown gene expression to test their function. Stem cells can also be cultured in a mammopad to investigate their properties and to investigate the contribution of stem cells to aberrant growth. Such a model has not been attempted before and there will be a number of challenges. However, should this project be successful, it may be possible to use the engineered tissue to replace surgically removed tissue or to introduce therapeutic reagents directly into the breast.