工程化肾组织作为药代动力学和肾毒性测试的潜在平台。
Engineered renal tissue as a potential platform for pharmacokinetic and nephrotoxicity testing.
作者信息
Davies Jamie
机构信息
University of Edinburgh, United Kingdom.
出版信息
Drug Discov Today. 2014 Jun;19(6):725-9. doi: 10.1016/j.drudis.2013.10.023. Epub 2013 Nov 4.
Abstract
Pharmacology and regenerative medicine interact in two ways. One is the use of drugs to promote tissue regeneration. The other, less obvious but with great potential, is the use of techniques developed for regenerative medicine to engineer realistic human organoids for drug screening. This review focuses on testing for nephrotoxicity, often a problem with drugs and poorly predicted in animals. Current human-based screens mainly use proximal tubule cells growing in 2D monolayers. Realism might be improved by collagen-based culture systems that encourage proximal tubule cells to grow as tubules. More realistic would be a recently developed technique for engineering functioning 'mini-kidneys' from suspensions of stem cells, a technique that works in mouse but that could also be applied to humans.
摘要
药理学与再生医学以两种方式相互作用。一种是使用药物促进组织再生。另一种方式不太明显但潜力巨大，即利用再生医学所开发的技术构建逼真的人体类器官用于药物筛选。本综述聚焦于肾毒性测试，肾毒性常常是药物存在的一个问题，且在动物实验中难以准确预测。当前基于人体的筛选主要使用在二维单层培养的近端小管细胞。基于胶原蛋白的培养系统或许能提高真实性，该系统可促使近端小管细胞生长为小管。更逼真的是一项最近开发的技术，即利用干细胞悬液构建具有功能的“微型肾脏”，该技术已在小鼠实验中成功应用，也有望应用于人类。
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