Department of Biomedical Engineering, Duke University, 136 Hudson Hall, PO Box 90281, Durham, North Carolina 27708, USA.
J Pharm Sci. 2011 Jan;100(1):59-74. doi: 10.1002/jps.22257. Epub 2010 Jun 8.
The use of animal models in drug discovery studies presents issues with feasibility and ethical concerns. To address these limitations, in vitro tissue models have been developed to provide a means for systematic, repetitive, and quantitative investigation of drugs. By eliminating or reducing the need for animal subjects, these models can serve as platforms for more tightly controlled, high-throughput screening of drugs and for pharmacokinetic and pharmacodynamic analyses of drugs. The focus of this review is three-dimensional (3D) tissue models that can capture cell-cell and cell-matrix interactions. Compared to the 2D culture of cell monolayers, 3D models more closely mimic native tissues since the cellular microenvironment established in the 3D models often plays a significant role in disease progression and cellular responses to drugs. A growing body of research has been published in the literature, which highlights the benefits of the 3D in vitro models of various tissues. This review provides an overview of some successful 3D in vitro models that have been developed to mimic liver, breast, cardiac, muscle, bone, and corneal tissues as well as malignant tissues in solid tumors.
在药物发现研究中使用动物模型存在可行性和伦理问题。为了解决这些限制，已经开发了体外组织模型，以提供一种系统、重复和定量研究药物的方法。通过消除或减少对动物实验对象的需求，这些模型可以作为更严格控制、高通量筛选药物的平台，并用于药物的药代动力学和药效学分析。本文综述的重点是能够捕捉细胞-细胞和细胞-基质相互作用的三维（3D）组织模型。与单层细胞的 2D 培养相比，3D 模型更能模拟天然组织，因为在 3D 模型中建立的细胞微环境通常在疾病进展和细胞对药物的反应中起着重要作用。越来越多的研究已经在文献中发表，这突出了各种组织的 3D 体外模型的优势。本文综述了一些成功开发的 3D 体外模型，这些模型模拟了肝脏、乳腺、心脏、肌肉、骨骼和角膜组织以及实体瘤中的恶性组织。
