A 3-D organoid kidney culture model engineered for high-throughput nephrotoxicity assays
A 3-D organoid kidney culture model engineered for high-throughput nephrotoxicity assays
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DOI：
10.1016/j.biomaterials.2012.02.063
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发表时间：
2012-06-01
期刊：
影响因子：
14
通讯作者：
Grainger, David W.
中科院分区：
文献类型：
--
作者：
Astashkina, Anna I.;Mann, Brenda K.;Grainger, David W.
细胞-细胞和细胞-基质相互作用控制体内细胞表型和功能。在体外维持这些相互作用对于在药物功效和毒性筛选的背景下产生和保持培养细胞对正常表型和功能的保真度是至关重要的。在培养塑料上的二维（2-D）培养物很少重现这些期望条件中的任何一个。三维（3-D）培养系统提供了传统的，但往往不相关的，在体外细胞培养和更准确的，但昂贵的，在体内模型之间的关键连接。本研究描述了肾近端小管（PT）的类器官衍生的3-D培养物的开发，其在组织环境中维持天然细胞相互作用，在体外调节原代细胞的表型稳定性长达6周。此外，与塑料上的永生化细胞不同，这些3-D类器官肾培养物对肾毒性剂暴露提供了更具生理相关性的反应，并在体内产生毒性生物标志物。这种仿生原代肾脏模型具有广泛的适用性，高通量药物和生物标志物肾毒性筛选，以及更多的机制药物毒理学，药理学和代谢研究。(C)2012爱思唯尔有限公司保留所有权利。
Cell cell and cell-matrix interactions control cell phenotypes and functions in vivo. Maintaining these interactions in vitro is essential to both produce and retain cultured cell fidelity to normal phenotype and function in the context of drug efficacy and toxicity screening. Two-dimensional (2-D) cultures on culture plastics rarely recapitulate any of these desired conditions. Three dimensional (3-D) culture systems provide a critical junction between traditional, yet often irrelevant, in vitro cell cultures and more accurate, yet costly, in vivo models. This study describes development of an organoid-derived 3-D culture of kidney proximal tubules (PTs) that maintains native cellular interactions in tissue context, regulating phenotypic stability of primary cells in vitro for up to 6 weeks. Furthermore, unlike immortalized cells on plastic, these 3-D organoid kidney cultures provide a more physiologically-relevant response to nephrotoxic agent exposure, with production of toxicity biomarkers found in vivo. This biomimetic primary kidney model has broad applicability to high-throughput drug and biomarker nephrotoxicity screening, as well as more mechanistic drug toxicology, pharmacology, and metabolism studies. (C) 2012 Elsevier Ltd. All rights reserved.