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Spheroids, organoids and kidneys-on-chips: how complex human cellular models have assisted in the study of kidney disease and renal ciliopathies
Microfluidics and Nanofluidics ( IF 2.3 ) Pub Date : 2023-02-17 , DOI: 10.1007/s10404-023-02629-4
Rebecca Marie Dewhurst , Elisa Molinari , John A. Sayer

Kidney disease is one of the leading causes of morbidity worldwide, emphasizing the importance for physiologically accurate disease models. With most of the approved renal drugs failing to perform as well in human clinical trials as they did in animal testing, it is imperative that new and improved human-based models are developed to test these potential therapeutics. One option is to use patient derived cell lines, grown in both two-dimensional (2D) and three-dimensional (3D) structures, known as spheroids and organoids. Despite their contributions to the field, the lack of physiological accuracy, including the absence of fluid flow, and mechanistic effects in these 2D and 3D models means there is still room for improvement. Organ-on-a-chip (OOAC) technology offers itself as a potential candidate model to overcome these limitations. Over recent years OOAC technology has grown in popularity, with multiple organ systems, including lung, liver, and kidney described in the literature. In this review, traditional human cellular based models, including monolayer, spheroid and organoid models will be discussed. Human kidney-on-a-chip models will also be discussed, while exploring the advantages and potential limitations of this rapidly emerging field for the study of human kidney disease and drug testing.



中文翻译:

球状体、类器官和片上肾脏:复杂的人体细胞模型如何帮助研究肾脏疾病和肾纤毛病

肾脏疾病是全球发病率的主要原因之一,强调了生理学上准确的疾病模型的重要性。由于大多数批准的肾脏药物在人体临床试验中的表现不如在动物试验中的表现,因此必须开发新的和改进的人体模型来测试这些潜在的治疗方法。一种选择是使用患者来源的细胞系,这些细胞系在二维 (2D) 和三维 (3D) 结构中生长,称为球状体和类器官。尽管它们对该领域做出了贡献,但这些 2D 和 3D 模型缺乏生理准确性,包括没有流体流动和机械效应,这意味着仍有改进的空间。器官芯片 (OOAC) 技术将自身作为克服这些限制的潜在候选模型。近年来,OOAC 技术越来越受欢迎,文献中描述了多个器官系统,包括肺、肝和肾。在这篇综述中,将讨论传统的基于人体细胞的模型,包括单层、球体和类器官模型。还将讨论人体肾脏芯片模型,同时探讨这一迅速兴起的领域在人类肾脏疾病研究和药物测试方面的优势和潜在局限性。

更新日期:2023-02-17
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