Engineered Kidney Tubules for Modeling Patient-Specific Diseases and Drug Discovery
Engineered Kidney Tubules for Modeling Patient-Specific Diseases and Drug Discovery
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DOI：
10.1016/j.ebiom.2018.06.005
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发表时间：
2018-07-01
期刊：
影响因子：
11.1
通讯作者：
Xinaris, Christodoulos
中科院分区：
文献类型：
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作者：
Benedetti, Valentina;Brizi, Valerio;Xinaris, Christodoulos
缺乏能够在体外忠实地复制复杂肾脏结构的工程系统，使得有效地模拟肾脏疾病和发育变得困难。使用聚二甲基硅氧烷（PDMS）支架和肾源性细胞系，我们开发了一种系统，可以快速设计具有典型肾上皮特性的定制3D小管。该系统已成功用于设计患者特异性小管，建立多囊肾病（PKD）模型，测试药物疗效，并确定潜在的新药物治疗方法。通过优化我们的系统，我们利用人诱导多能干细胞（iPSCs）构建了功能性输尿管芽样小管，并鉴定出了能像胚胎肾脏一样诱导出芽形态发生的生长因子组合。最后，我们应用该试验研究了来自PAX2突变患者的ub样小管的出芽缺陷。我们的系统使人类肾脏疾病和发展的建模，药物测试和发现，并为工程解剖正确的肾脏组织在体外和开发个性化的医疗应用奠定了基础。(C) 2018年作者。Elsevier B.V.出版
The lack of engineering systems able to faithfully reproduce complex kidney structures in vitro has made it difficult to efficiently model kidney diseases and development. Using polydimethylsiloxane (PDMS) scaffolds and a kidney-derived cell line we developed a system to rapidly engineer custom-made 3D tubules with typical renal epithelial properties. This system was successfully employed to engineer patient-specific tubules, to model polycystic kidney disease (PKD) and test drug efficacy, and to identify a potential new pharmacological treatment. By optimizing our system we constructed functional ureteric bud (UB)-like tubules from human induced pluripotent stem cells (iPSCs), and identified a combination of growth factors that induces budding morphogenesis like embryonic kidneys do. Finally, we applied this assay to investigate budding defects in UB-like tubules derived from a patient with a PAX2 mutation.Our system enables the modeling of human kidney disease and development, drug testing and discovery, and lays the groundwork for engineering anatomically correct kidney tissues in vitro and developing personalized medicine applications. (C) 2018 The Authors. Published by Elsevier B.V.