肾微生理模型用于肾毒性评估

IF 6.1 Q1 TOXICOLOGY Current Opinion in Toxicology Pub Date : 2022-06-01 DOI:10.1016/j.cotox.2022.03.002
Anish Mahadeo , Catherine K. Yeung , Jonathan Himmelfarb , Edward J. Kelly
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引用次数: 2

摘要

肾毒性测试是新分子实体(NMEs)临床前开发的重要步骤,传统上在二维细胞培养系统和动物模型中进行。然而,二维培养系统无法复制复杂的体内微环境,动物模型面临包括药物转运体过表达在内的种间差异。在过去的十年中,3D微生理系统(MPS)的发展解决了这些问题。本文就肾脏MPS及其在药物毒性检测和肾脏疾病研究中的应用进展进行综述。我们发现目前的研究在解决MPS的局限性方面取得了重大进展,如吞吐量,纳入肾单位的各个区域,如肾小球,并成功地建模和预测当前和新药的临床相关肾毒性。
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Kidney microphysiological models for nephrotoxicity assessment

Nephrotoxicity testing is an important step in preclinical development of new molecular entities (NMEs) and has traditionally been performed in 2D cell culture systems and animal models. However, 2D culture systems fail to replicate complex in vivo microenvironment and animal models face interspecies differences including the overexpression of drug transporters. In the last decade, 3D microphysiological systems (MPS) have been developed to address these concerns. Here, we review recent advancements in kidney MPS and their application in drug-induced toxicity testing and kidney disease research. We find that current research is making significant progress addressing MPS limitations such as throughput, incorporating various regions of the nephron such as the glomerulus, and successfully modeling and predicting clinically relevant nephrotoxicity of current and new drugs.

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来源期刊
Current Opinion in Toxicology
Current Opinion in Toxicology Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
10.40
自引率
0.00%
发文量
43
期刊介绍: The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students. Division of the subject into sections: For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year: Mechanistic Toxicology, Metabolic Toxicology, Risk assessment in Toxicology, Genomic Toxicology, Systems Toxicology, Translational Toxicology.
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