Engineering an in vitro model of the mammary gland

乳房（乳腺）是一个复杂的，高度特化的组织，它已经进化到为年轻人提供营养。乳房这一重要的赋予生命的作用并非没有给母亲带来代价，因为乳腺组织极易患癌症，乳腺癌是妇女最可能死亡的形式之一。人类的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周期性变化。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周期。据估计，在怀孕期间，由于激素和其他分泌因素的影响，上皮细胞的数量增加了大约100倍。我们目前对这些复杂的细胞组成和功能变化过程的了解来自于实验动物，主要是小鼠。有可能对老鼠进行基因改造，使它们“失去”某一特定基因的功能，从而使该基因在乳房发育中的作用得以确定，并在分子水平上进行研究。这只老鼠也被广泛用于肿瘤发展的研究，并被用作乳腺癌的模型。这个项目的目的是设计一个可以在培养中生长的乳腺模型，这样就可以大大减少对啮齿动物的使用。如果这个项目成功，我们还将开发这个模型的人类版本，以便在与人类疾病最相关的组织中进行研究。当测试新的治疗药物时，这一点尤其重要，因为这些药物可能有意想不到的副作用，或者在啮齿类动物和人类身上的效果可能不同。这个项目将结合剑桥大学两个系的技能：材料科学与冶金系和病理学系。这将汇集组织工程和乳腺生物学方面的专业知识。目的是建立一个聚合物支架，脂肪细胞和乳腺上皮细胞都可以在其中生长，随后用各种试剂处理以诱导生长和分支。一旦形成，可以用诱导或抑制基因表达的药物来治疗乳腺细胞，以测试它们的功能。干细胞也可以在哺乳动物中培养，以研究它们的特性，并研究干细胞对异常生长的贡献。这种模式以前从未尝试过，将面临许多挑战。然而，如果这个项目成功，可能会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.