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在药物发现和开发中使用微生理系统对药物诱导的损伤进行先进的体外评估

Hiroshi Arakawa¹, Kohei Matsushita², Naoki Ishiguro³

¹Faculty of Pharmaceutical Sciences, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.

Drug metabolism and pharmacokinetics

|March 15, 2025

概括

开发使用人类附近管状上皮细胞 (RPTEC) 的新体外方法对于准确预测药物诱导损伤 (DIKI) 和提高药物安全至关重要.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
毒理学毒理学毒理学
再生医学是一种再生医学.

背景情况:

药物诱导损伤 (DIKI) 是急性损伤 (AKI) 的重要原因之一.
目前的体外试验模型往往无法准确预测人类DIKI,原因是生理功能受损.
脏靠近管状上皮细胞 (RPTEC) 是DIKI的关键点,因为它们的药物载体表达很高.

研究的目的:

审查使用人类RPTECs评估DIKI的先进体外方法.
突出改善细胞培养系统对DIKI预测的重要性.
讨论细胞工程和再生医学在DIKI评估中的作用.

主要方法:

复习先进的细胞培养系统,包括微生理系统和芯片上的器官.
讨论三维 (3D) 培养的RPTEC和来自诱导多能干细胞 (iPS) 的器官.
专注于增强药物载体表达和预测性能的系统.

主要成果:

与传统单层培养相比,3D培养的RPTEC表现出增强的药物载体表达和更好的预测能力.
共同培养系统,如肝脏脏器官在芯片上,可以检测药物代谢物诱导的毒性.
已建立的器官系统为DIKI研究提供了更具生理相关性的模型.

结论:

先进的体外系统,特别是使用3D RPTEC,微生理系统和器官的系统,对准确的DIKI评估有很大的前景.
这些新的方法解决了传统细胞培养和动物试验的局限性,与福利问题以及对人类相关预测的需求保持一致.
这些系统的进一步开发和实施对于更安全的药物发现和开发至关重要.

关键词:

药物诱导的损伤是药物诱导的在体外实验方法.脏 - 脏 - 脏微生物系统微生物系统.球形球形是指一个球形状的球体.运输商运输商运输商

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