Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments

被引:154
作者
Astashkina, Anna [1 ]
Grainger, David W. [1 ]
机构
[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
关键词
Toxicity; Drug development; Nanotoxicity; Reasons for failure; Cell culture models; HTS screens; Cellular microenvironment; 3-D organoid culture; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; TISSUE-CULTURE; PANCREATIC-CANCER; GENE-EXPRESSION; 3-DIMENSIONAL CULTURE; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; LIVER-CELLS; POLARIZED EPITHELIUM;
D O I
10.1016/j.addr.2014.02.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Drug failure due to toxicity indicators remains among the primary reasons for staggering drug attrition rates during clinical studies and post-marketing surveillance. Broader validation and use of next-generation 3-D improved cell culture models are expected to improve predictive power and effectiveness of drug toxicological predictions. However, after decades of promising research significant gaps remain in our collective ability to extract quality human toxicity information from in vitro data using 3-D cell and tissue models. Issues, challenges and future directions for the field to improve drug assay predictive power and reliability of 3-D models are reviewed. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 18
页数:18
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