Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening.
Biomimetic 3D Tissue Models for Advanced High-Throughput Drug Screening.
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DOI：
10.1177/2211068214557813
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Nam KH;Smith AS;Lone S;Kwon S;Kim DH
目前用于识别新候选药物的大多数药物筛选分析都是基于2D细胞的系统，尽管这种体外分析不能充分重现3D组织的体内复杂性。在临床前试验中对人体组织环境的不充分代表可能导致对整体组织功能的复合效应的不准确预测。通过关注单一途径或蛋白质靶点来筛选化合物功效，再加上长期维持2D单层的困难，当利用这种简单的模型系统进行生理药物筛选应用时，可能会加剧这些问题。大量研究表明，在体内组织功能建模方面，3D培养中的细胞对药物的反应比2D培养中的细胞反应更好，这凸显了使用3D模型进行临床前药物筛选的优势。在这篇综述中，我们讨论了微工程3D组织模型的发展，这些模型准确地模拟了天然组织样本的生理特性，并强调了在未来的药物筛选应用中，使用这种3D微组织模型比传统的基于细胞的分析有优势。我们还讨论了基于工程组织的仿生3D环境，作为开发针对特定疾病模型的更具预测性的药物筛选分析的潜在临床前模型。
Most current drug screening assays used to identify new drug candidates are 2D cell-based systems, even though such in vitro assays do not adequately recreate the in vivo complexity of 3D tissues. Inadequate representation of the human tissue environment during a preclinical test can result in inaccurate predictions of compound effects on overall tissue functionality. Screening for compound efficacy by focusing on a single pathway or protein target, coupled with difficulties in maintaining long-term 2D monolayers, can serve to exacerbate these issues when utilizing such simplistic model systems for physiological drug screening applications. Numerous studies have shown that cell responses to drugs in 3D culture are improved from those in 2D, with respect to modeling in vivo tissue functionality, which highlights the advantages of using 3D-based models for preclinical drug screens. In this review, we discuss the development of microengineered 3D tissue models which accurately mimic the physiological properties of native tissue samples, and highlight the advantages of using such 3D micro-tissue models over conventional cell-based assays for future drug screening applications. We also discuss biomimetic 3D environments, based-on engineered tissues as potential preclinical models for the development of more predictive drug screening assays for specific disease models.
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