Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy.
Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy.
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在芯片上开发器官水平的功能性肾小球以模拟高血压肾病
DOI：
10.1038/srep31771
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发表时间：
2016-08-25
影响因子：
4.6
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Zhou M;Zhang X;Wen X;Wu T;Wang W;Yang M;Wang J;Fang M;Lin B;Lin H
肾小球高血压是使肾小球疾病恶化为终末期肾病的重要因素，因为其最终导致肾小球硬化（特别是在高血压和糖尿病肾病中）。肾小球高血压引起的肾小球硬化的确切机制尚不清楚，部分原因是缺乏能够模拟和调节复杂机械力和/或器官水平疾病过程的合适的体外或体内模型。我们开发了一种“芯片上肾小球”（GC）微流体装置。该设备重建具有器官水平肾小球功能的肾小球，以创建模拟人类高血压肾病的芯片上的疾病模型。它包括两个通道，由肾小球内皮细胞和足细胞的紧密相对层排列，所述肾小球内皮细胞和足细胞经历生理条件的流体流动以模拟体内肾小球微环境。我们的研究结果表明，肾小球机械力在细胞骨架重排以及细胞及其连接的损伤中起着至关重要的作用，这些损伤导致高血压肾病中观察到的肾小球渗漏增加。结果还表明，GC可以容易和灵活地满足肾脏疾病模型的要求。GC可以提供药物筛选和毒理学测试，并为肾小球疾病创造潜在的新的个性化和准确的治疗平台。
Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a “glomerulus-on-a-chip” (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.