Vascular organs-on-chip made with patient-derived endothelial cells: technologies to transform drug discovery and disease modeling.

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Discovery Pub Date : 2024-03-01 Epub Date: 2023-12-20 DOI:10.1080/17460441.2023.2294947
Chloe P Whitworth, William J Polacheck
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Abstract

Introduction: Vascular diseases impart a tremendous burden on healthcare systems in the United States and across the world. Efforts to improve therapeutic interventions are hindered by limitations of current experimental models. The integration of patient-derived cells with organ-on-chip (OoC) technology is a promising avenue for preclinical drug screening that improves upon traditional cell culture and animal models.

Areas covered: The authors review induced pluripotent stem cells (iPSC) and blood outgrowth endothelial cells (BOEC) as two sources for patient-derived endothelial cells (EC). They summarize several studies that leverage patient-derived EC and OoC for precision disease modeling of the vasculature, with a focus on applications for drug discovery. They also highlight the utility of patient-derived EC in other translational endeavors, including ex vivo organogenesis and multi-organ-chip integration.

Expert opinion: Precision disease modeling continues to mature in the academic space, but end-use by pharmaceutical companies is currently limited. To fully realize their transformative potential, OoC systems must balance their complexity with their ability to integrate with the highly standardized and high-throughput experimentation required for drug discovery and development.

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利用源自患者的内皮细胞制造芯片上的血管器官:改变药物发现和疾病建模的技术。
导言:血管疾病给美国和全世界的医疗保健系统带来了巨大负担。当前实验模型的局限性阻碍了改进治疗干预措施的努力。将患者来源细胞与芯片器官(OoC)技术相结合是临床前药物筛选的一个很有前景的途径,它改进了传统的细胞培养和动物模型:作者综述了诱导多能干细胞(iPSC)和血液生长内皮细胞(BOEC)这两种患者内皮细胞(EC)来源。他们总结了几项利用患者来源的内皮细胞和OoC进行血管精准疾病建模的研究,重点是药物发现方面的应用。他们还强调了患者来源的EC在其他转化工作中的实用性,包括体外器官生成和多器官芯片整合:精准疾病建模在学术领域不断走向成熟,但制药公司的终端应用目前还很有限。要充分发挥其变革潜力,OoC 系统必须在其复杂性与药物发现和开发所需的高度标准化和高通量实验整合能力之间取得平衡。
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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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