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基于类器官的药物发现进展:革新精准医学与药理学

Advancements in Organoid-Based Drug Discovery: Revolutionizing Precision Medicine and Pharmacology.

作者信息

Singh Dilpreet, Thakur Akshay, Kumar Akshay

机构信息

School of Pharmaceutical Sciences, CT University, Ludhiana, Punjab, India.

出版信息

Drug Dev Res. 2025 Jun;86(4):e70121. doi: 10.1002/ddr.70121.

Abstract

Organoids, 3D cellular models derived from stem cells, have revolutionized drug testing by providing human-relevant systems for modeling diseases and testing drug efficacy. Unlike traditional 2D cell cultures or animal models, organoids closely resemble the complex architecture and function of human tissues, offering more accurate predictions of drug responses. Researchers are increasingly utilizing these models in oncology, neurology, liver toxicity, and personalized medicine. Recent advances in gene editing (e.g., CRISPR-Cas9), multi-omics technologies, and organoid-on-chip systems have further enhanced the capabilities of organoids in drug discovery. CRISPR-Cas9 allows for precise modeling of genetic disorders, while multi-omics approaches integrate transcriptomics, proteomics, and metabolomics to provide deeper insights into drug metabolism and toxicity. Organoid-on-chip platforms combine organoid culture with microfluidic systems, enabling the simulation of organ interactions and real-time drug testing. AI and machine learning models now enhance these platforms by predicting drug responses and optimizing high-throughput screening. Despite these advancements, challenges such as scalability, reproducibility, and the incomplete recapitulation of complex organ functions remain. Organoids hold the promise of significantly reducing reliance on animal models, improving the accuracy of drug testing, and paving the way for personalized treatments. This review outlines the latest innovations in organoid-based drug discovery, highlighting their potential to transform modern pharmacology and precision medicine, while acknowledging the ongoing efforts to address existing limitations.

摘要

类器官是源自干细胞的三维细胞模型,通过提供与人类相关的疾病建模和药物疗效测试系统,彻底改变了药物测试。与传统的二维细胞培养或动物模型不同,类器官与人类组织的复杂结构和功能非常相似,能更准确地预测药物反应。研究人员越来越多地在肿瘤学、神经学、肝脏毒性和个性化医疗中使用这些模型。基因编辑(如CRISPR-Cas9)、多组学技术和芯片类器官系统的最新进展进一步增强了类器官在药物发现中的能力。CRISPR-Cas9可实现遗传疾病的精确建模,而多组学方法整合了转录组学、蛋白质组学和代谢组学,以更深入地了解药物代谢和毒性。芯片类器官平台将类器官培养与微流控系统相结合,能够模拟器官间相互作用并进行实时药物测试。人工智能和机器学习模型现在通过预测药物反应和优化高通量筛选来增强这些平台。尽管取得了这些进展,但仍存在可扩展性、可重复性以及复杂器官功能模拟不完整等挑战。类器官有望显著减少对动物模型的依赖,提高药物测试的准确性,并为个性化治疗铺平道路。本综述概述了基于类器官的药物发现的最新创新,强调了它们在改变现代药理学和精准医学方面的潜力,同时也认可了为解决现有局限性所做的持续努力。

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