微生理系统在新药模式的毒性测试中的机遇
Tengku Ibrahim Maulana1,2, Nienke R Wevers3, Theodora Kristoforus1
1Department for Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.
Annual review of pharmacology and toxicology
|September 3, 2024
概括
新的药物模式可能会导致复杂的副作用. 微生理系统 (MPS) 提供了一个有希望的体外方法来模拟这些毒性,克服了动物研究的局限性,以更好地评估药物安全性.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 生物技术和生物工程 生物技术和生物工程
- 药物开发与安全问题
背景情况:
- 新型药物模式为以前无法治疗的目标提供了访问权限,提供了显著的治疗潜力.
- 这些新药往往表现出复杂的,不可预测的,人类特有的副作用,对药物开发构成挑战.
- 由于可翻译性问题,传统的动物研究对人类毒性的预测价值有限,需要使用替代方法.
研究的目的:
- 审查微生理系统 (MPS) 在建模与新药模式相关的毒理过程中的应用.
- 评估MPS在预测特定不良事件方面的潜力,包括周围神经病变,血栓细胞减小,免疫中介性肝毒性和细胞因子释放综合征.
- 突出MPS在解决传统临床前毒性测试局限性的能力.
主要方法:
- 审查利用微生理系统 (MPS) 进行毒理学评估的现有研究.
- 专注于MPS功能,使复杂的生物反应能够在体外建模:可调节的细胞复杂性 (包括免疫细胞),可修改的组织结构,动态机制监测和多器官连接.
- 在与新药模式相关的四个特定临床不良事件的背景下分析MPS性能.
主要成果:
- 微生理系统 (MPS) 为模拟复杂的毒理学过程提供了关键功能,包括细胞和组织架构定制,动态监测和器官间系统集成.
- 对于模拟外围神经病变,血小板减少,免疫中介性肝毒性和细胞因子释放综合征等不良事件,已经探索了MPS.
- 审查表明,虽然MPS用于新药毒性测试的使用正在出现,但它显示出显著的潜力.
结论:
- 微生理系统 (MPS) 是一种强大的体外工具,用于建模与新型药物模式相关的复杂毒性.
- 对于预测人类特异性不良事件而言,MPS能力,如结合免疫组件和多器官连接,至关重要.
- 尽管处于早期阶段,但MPS显示出强大的未来潜力,可以改善药物安全性评估并克服制药研究中动物模型的局限性.
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