Engineering an in vitro model of the mammary gland

乳房（乳腺）是一个复杂的，高度专业化的组织，已经进化为年轻人提供营养。乳房的这种重要的生命赋予作用对母亲来说并非没有代价，因为这种组织极易患癌症，乳腺癌是妇女最可能的死亡形式之一。人类乳房在成年器官中是不寻常的，因为它在雌性动物的一生中经历了戏剧性的和周期性的变化。随着每次连续怀孕，乳腺细胞经历增殖、分化、分泌和程序性细胞死亡的循环。据估计，在怀孕期间，上皮细胞的数量会因激素和其他分泌因子而增加约100倍。我们目前对细胞组成和功能的这些复杂变化过程的了解来自于对实验动物的使用，主要是小鼠。有可能对小鼠进行遗传修饰，使它们“失去”特定基因的功能，从而在分子水平上定义和研究该基因在乳房发育中的作用。小鼠也被广泛用于肿瘤发展的研究，并被用作乳腺癌的模型。该项目的目的是设计一种可以在培养物中生长的乳腺模型，以便可以大大减少啮齿动物的使用。如果该项目成功，我们还将开发该模型的人类版本，以便在与人类疾病最相关的组织中进行研究。这在测试可能具有不期望的副作用或与人类相比在啮齿动物中可能不同的新治疗药物时尤为重要。这个项目将联合收割机的技能，两个部门在剑桥：材料科学和冶金学系和病理学系。这将汇集组织工程和乳腺生物学方面的专业知识。其目的是建立一种聚合物支架，其中脂肪细胞和乳腺上皮细胞都可以生长，随后用各种试剂处理以诱导生长和分支。一旦形成，可以用诱导或敲低基因表达的试剂处理乳房衬垫以测试其功能。干细胞也可以在乳房垫中培养，以研究其特性并研究干细胞对异常生长的贡献。这种模式以前没有尝试过，而且会有一些挑战。然而，如果该项目成功，则可能使用工程组织来替代手术切除的组织或将治疗试剂直接引入乳房。

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.