Abstract：
Drug-induced liver injury (DILI) is the leading cause of compound attrition during drug development. Over the years, a battery of in-vitro cell culture toxicity tests is being conducted to evaluate the toxicity of compounds prior to testing in laboratory animals. Two-dimensional (2D) in-vitro cell culture models are commonly used and have provided a great deal of knowledge; however, these models often fall short in mimicking natural structures of tissues in-vivo. Testing in humans is the most logical method, but unfortunately there are ethical limitations associated with human tests. To overcome these limitations better human-relevant, predictive models are required. The past decade has witnessed significant efforts towards the development of three-dimensional (3D) in-vitro cell culture models better mimicking in-vivo physiology. 3D cell culture has advantages in being representative of the interactions of cells in-vivo and when validated can act as an interphase between 2D cell culture models and in-vivo animal models. The current review seeks to provide an overview of the challenges that make biomarkers used for detection of DILI not to be sensitive enough during drug development and explore how 3D cell culture models can be used to address the gap with the current models.
摘要：
药物诱导的肝损伤（DILI）是药物开发过程中化合物磨损的主要原因。多年来,在实验动物中进行测试之前，正在进行一系列体外细胞培养毒性测试，以评估化合物的毒性。通常使用二维（2D）体外细胞培养模型，并提供了大量知识；但是，这些模型通常无法在体内模拟组织的自然结构。在人类中测试是最合乎逻辑的方法，但不幸的是，人类测试存在道德限制。为了克服这些限制，更好地与人类相关，需要预测模型。在过去的十年中，人们做出了巨大的努力来开发三维（3D）体外细胞培养模型，以更好地模仿体内生理学。3D细胞培养在代表体内细胞的相互作用方面具有优势，并且在验证时可以充当2D细胞培养模型和体内动物模型之间的间期。当前的综述旨在概述使用于检测DILI的生物标志物在药物开发过程中不够敏感的挑战，并探索如何使用3D细胞培养模型来解决与当前模型的差距。
