The ultimate goal of most biomedical research is to gain greater insight into mechanisms of human disease or to develop new and improved therapies or diagnostics. Although great advances have been made in terms of developing disease models in animals, such as transgenic mice, many of these models fail to faithfully recapitulate the human condition. In addition, it is difficult to identify critical cellular and molecular contributors to disease or to vary them independently in whole-animal models. This challenge has attracted the interest of engineers, who have begun to collaborate with biologists to leverage recent advances in tissue engineering and microfabrication to develop novel in vitro models of disease. As these models are synthetic systems, specific molecular factors and individual cell types, including parenchymal cells, vascular cells, and immune cells, can be varied independently while simultaneously measuring system-level responses in real time. In this article, we provide some examples of these efforts, including engineered models of diseases of the heart, lung, intestine, liver, kidney, cartilage, skin and vascular, endocrine, musculoskeletal, and nervous systems, as well as models of infectious diseases and cancer. We also describe how engineered in vitro models can be combined with human inducible pluripotent stem cells to enable new insights into a broad variety of disease mechanisms, as well as provide a test bed for screening new therapies.

中文翻译：

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工程体外疾病模型。

大多数生物医学研究的最终目标是对人类疾病的机制有更深入的了解或开发新的和改进的疗法或诊断方法。尽管在开发动物（例如转基因小鼠）的疾病模型方面已经取得了很大的进步，但是这些模型中有许多无法如实地概括人类的状况。此外，很难确定导致疾病的关键细胞和分子因素，或者很难在整个动物模型中独立地改变它们。这一挑战吸引了工程师的兴趣，他们已开始与生物学家合作，以利用组织工程和微加工领域的最新进展来开发新颖的疾病体外模型。由于这些模型是合成系统，因此特定的分子因子和单个细胞类型（包括实质细胞，血管细胞，免疫细胞和免疫细胞可以独立变化，同时实时测量系统级响应。在本文中，我们提供了这些工作的一些示例，包括心脏，肺，肠，肝，肾，软骨，皮肤和血管，内分泌，肌肉骨骼和神经系统疾病的工程模型，以及传染病模型和癌症。我们还描述了如何将工程化的体外模型与人诱导型多能干细胞结合起来，以使人们能够深入了解各种疾病机制，并为筛选新疗法提供测试平台。肠，肝，肾，软骨，皮肤和血管，内分泌，肌肉骨骼和神经系统，以及传染病和癌症模型。我们还描述了如何将工程化的体外模型与人诱导型多能干细胞结合起来，以使人们能够深入了解各种疾病机制，并为筛选新疗法提供测试平台。肠，肝，肾，软骨，皮肤和血管，内分泌，肌肉骨骼和神经系统，以及传染病和癌症模型。我们还描述了如何将工程化的体外模型与人诱导型多能干细胞结合起来，以使人们能够深入了解各种疾病机制，并为筛选新疗法提供测试平台。