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Modeling Distal Convoluted Tubule (Patho)Physiology: An Overview of Past Developments and an Outlook Toward the Future
Tissue Engineering, Part C: Methods ( IF 3 ) Pub Date : 2021-03-15 , DOI: 10.1089/ten.tec.2020.0345
Charlotte J A Olde Hanhof 1 , Fjodor A Yousef Yengej 2, 3 , Maarten B Rookmaaker 3 , Marianne C Verhaar 3 , Jenny van der Wijst 1 , Joost G Hoenderop 1
Affiliation  

The kidneys are essential for maintaining electrolyte homeostasis. Blood electrolyte composition is controlled by active reabsorption and secretion processes in dedicated segments of the kidney tubule. Specifically, the distal convoluted tubule (DCT) and connecting tubule are important for regulating the final excretion of sodium, magnesium, and calcium. Studies unravelling the specific function of these segments have greatly improved our understanding of DCT (patho)physiology. Over the years, experimental models used to study the DCT have changed and the field has advanced from early dissection studies with rats and rabbits to the use of various transgenic mouse models. Developments in dissection techniques and cell culture methods have resulted in immortalized mouse DCT cell lines and made it possible to specifically obtain DCT fragments for ex vivo studies. However, we still do not fully understand the complex (patho)physiology of this segment and there is need for advanced human DCT models. Recently, kidney organoids and tubuloids have emerged as new complex cell models that provide excellent opportunities for physiological studies, disease modeling, drug discovery, and even personalized medicine in the future. This review presents an overview of cell models used to study the DCT and provides an outlook on kidney organoids and tubuloids as model for DCT (patho)physiology.

中文翻译:

模拟远曲小管(病理)生理学:过去发展的概述和对未来的展望

肾脏对于维持电解质稳态至关重要。血液电解质成分受肾小管特定节段的主动重吸收和分泌过程控制。具体来说,远曲小管 (DCT) 和连接小管对于调节钠、镁和钙的最终排泄很重要。阐明这些节段特定功能的研究极大地提高了我们对 DCT(病理)生理学的理解。多年来,用于研究 DCT 的实验模型发生了变化,该领域已经从早期的大鼠和兔解剖研究发展到使用各种转基因小鼠模型。解剖技术和细胞培养方法的发展已经产生了永生化的小鼠 DCT 细胞系,并使特异性获得 DCT 片段成为可能。离体研究。然而,我们仍然不完全了解这一部分的复杂(病理)生理学,需要先进的人类 DCT 模型。最近,肾脏类器官和肾小管已成为新的复杂细胞模型,为未来的生理研究、疾病建模、药物发现甚至个性化医疗提供了绝佳的机会。本综述概述了用于研究 DCT 的细胞模型,并提供了肾脏类器官和管状体作为 DCT(病理)生理学模型的前景。
更新日期:2021-03-18
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