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器官芯片技术:攻克遗传性肾脏疾病的新工具。

Organs-on-chip technology: a tool to tackle genetic kidney diseases.

机构信息

Div. Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.

出版信息

Pediatr Nephrol. 2022 Dec;37(12):2985-2996. doi: 10.1007/s00467-022-05508-2. Epub 2022 Mar 14.

Abstract

Chronic kidney disease (CKD) is a major healthcare burden that takes a toll on the quality of life of many patients. Emerging evidence indicates that a substantial proportion of these patients carry a genetic defect that contributes to their disease. Any effort to reduce the percentage of patients with a diagnosis of nephropathy heading towards kidney replacement therapies should therefore be encouraged. Besides early genetic screenings and registries, in vitro systems that mimic the complexity and pathophysiological aspects of the disease could advance the screening for targeted and personalized therapies. In this regard, the use of patient-derived cell lines, as well as the generation of disease-specific cell lines via gene editing and stem cell technologies, have significantly improved our understanding of the molecular mechanisms underlying inherited kidney diseases. Furthermore, organs-on-chip technology holds great potential as it can emulate tissue and organ functions that are not found in other, more simple, in vitro models. The personalized nature of the chips, together with physiologically relevant read-outs, provide new opportunities for patient-specific assessment, as well as personalized strategies for treatment. In this review, we summarize the major kidney-on-chip (KOC) configurations and present the most recent studies on the in vitro representation of genetic kidney diseases using KOC-driven strategies.

摘要

慢性肾脏病(CKD)是一个主要的医疗保健负担,对许多患者的生活质量造成影响。新出现的证据表明,相当一部分患者存在导致其疾病的遗传缺陷。因此,应鼓励减少被诊断为肾病并走向肾脏替代疗法的患者比例。除了早期的基因筛查和登记外,模拟疾病复杂性和病理生理方面的体外系统可以推进针对目标和个性化治疗的筛选。在这方面,使用患者来源的细胞系,以及通过基因编辑和干细胞技术生成疾病特异性细胞系,大大提高了我们对遗传性肾脏疾病潜在分子机制的理解。此外,器官芯片技术具有很大的潜力,因为它可以模拟在其他更简单的体外模型中找不到的组织和器官功能。芯片的个性化以及与生理相关的读出提供了针对患者进行特定评估以及针对治疗的个性化策略的新机会。在这篇综述中,我们总结了主要的肾脏芯片(KOC)配置,并介绍了使用 KOC 驱动策略在体外代表遗传肾脏疾病的最新研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9636/9587109/a5db880d6aea/467_2022_5508_Fig1_HTML.jpg

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