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芯片上的肾脏:未开发的机遇。

Kidney-on-a-chip: untapped opportunities.

机构信息

Division of Plastic Surgery, Department of Surgery, Oulu University Hospital, Oulu, Finland; Biotechnology Research Center, Libyan Authority for Research, Science and Technology, Tripoli, Libya.

Division of Nephrology, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

出版信息

Kidney Int. 2018 Dec;94(6):1073-1086. doi: 10.1016/j.kint.2018.06.034. Epub 2018 Oct 23.

Abstract

The organs-on-a-chip technology has shown strong promise in mimicking the complexity of native tissues in vitro and ex vivo, and recently significant advances have been made in applying this technology to studies of the kidney and its diseases. Individual components of the nephron, including the glomerulus, proximal tubule, and distal tubule/medullary collecting duct, have been successfully mimicked using organs-on-a-chip technology and yielding strong promises in advancing the field of ex vivo drug toxicity testing and augmenting renal replacement therapies. Although these models show promise over 2-dimensional cell systems in recapitulating important nephron features in vitro, nephron functions, such as tubular secretion, intracellular metabolism, and renin and vitamin D production, as well as prostaglandin synthesis are still poorly recapitulated in on-chip models. Moreover, construction of multiple-renal-components-on-a-chip models, in which various structures and cells of the renal system interact with each other, has remained a challenge. Overall, on-chip models show promise in advancing models of normal and pathological renal physiology, in predicting nephrotoxicity, and in advancing treatment of chronic kidney diseases.

摘要

器官芯片技术在体外和体内模拟天然组织的复杂性方面显示出了强大的潜力,最近在将该技术应用于肾脏及其疾病的研究方面取得了重大进展。肾单位的各个组成部分,包括肾小球、近端肾小管和远端肾小管/髓质集合管,已经成功地通过器官芯片技术进行了模拟,并在推进体外药物毒性测试领域和增强肾脏替代疗法方面展现出了巨大的潜力。尽管这些模型在 2 维细胞系统中具有更好的重现重要肾单位特征的潜力,但在芯片模型中,肾单位功能(如管状分泌、细胞内代谢、肾素和维生素 D 的产生以及前列腺素的合成)仍然不能很好地重现。此外,构建具有多个肾单位的芯片模型,其中肾脏系统的各种结构和细胞相互作用,仍然是一个挑战。总的来说,芯片模型在推进正常和病理生理肾脏生理学模型、预测肾毒性以及推进慢性肾脏疾病治疗方面具有广阔的前景。

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