Bioengineered kidney tubules efficiently excrete uremic toxins.
Bioengineered kidney tubules efficiently excrete uremic toxins.
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DOI：
10.1038/srep26715
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发表时间：
2016-05-31
影响因子：
4.6
通讯作者：
Masereeuw R
中科院分区：
文献类型：
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作者：
Jansen J;Fedecostante M;Wilmer MJ;Peters JG;Kreuser UM;van den Broek PH;Mensink RA;Boltje TJ;Stamatialis D;Wetzels JF;van den Heuvel LP;Hoenderop JG;Masereeuw R
开发用于去除废物（例如尿毒症毒素）的生物技术平台是改善患有终末期肾病（ESRD）的患者的当前治疗方式的先决条件，所述废物通常与血浆中的蛋白质结合。在这里，我们提出了一种新设计的生物工程肾小管能够主动尿毒症毒素分泌通过协调行动的基本肾脏转运蛋白，即有机阴离子转运蛋白1（OAT 1），乳腺癌耐药蛋白（BCRP）和多药耐药蛋白4（MRP 4）。证明了人条件永生化近端小管上皮细胞（ciPTEC）在具有维持的屏障功能的生物功能化中空纤维上的三维细胞单层形成。使用定制的流动系统，证实了人血清白蛋白结合的尿毒症毒素、硫酸吲哚酚和犬尿烯酸的分泌清除以及白蛋白跨肾小管的重吸收。这些功能性生物工程肾小管在肾脏替代疗法和再生医学以及药物开发计划中是有前途的实体。
The development of a biotechnological platform for the removal of waste products (e.g. uremic toxins), often bound to proteins in plasma, is a prerequisite to improve current treatment modalities for patients suffering from end stage renal disease (ESRD). Here, we present a newly designed bioengineered renal tubule capable of active uremic toxin secretion through the concerted action of essential renal transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug resistance protein-4 (MRP4). Three-dimensional cell monolayer formation of human conditionally immortalized proximal tubule epithelial cells (ciPTEC) on biofunctionalized hollow fibers with maintained barrier function was demonstrated. Using a tailor made flow system, the secretory clearance of human serum albumin-bound uremic toxins, indoxyl sulfate and kynurenic acid, as well as albumin reabsorption across the renal tubule was confirmed. These functional bioengineered renal tubules are promising entities in renal replacement therapies and regenerative medicine, as well as in drug development programs.