Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Key Laboratory of Kidney Disease of Liaoning Province, The Center for the Transformation Medicine of Kidney Disease of Liaoning Province, No. 222 Zhongshan Road, Dalian 116011, China.
Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, No. 457 Zhongshan Road, Dalian 116023, China.
Sci Rep. 2016 Aug 25;6:31771. doi: 10.1038/srep31771.
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.
肾小球高血压是加重肾小球疾病向终末期肾病发展的一个重要因素，因为它最终会导致肾小球硬化（尤其是在高血压和糖尿病肾病中）。肾小球高血压引起肾小球硬化的确切机制尚不清楚，部分原因是缺乏合适的体外或体内模型来模拟和调节复杂的机械力和/或器官水平的疾病过程。我们开发了一种“肾小球芯片”（GC）微流控装置。该装置通过器官水平的肾小球功能重新构建肾小球，以创建一种芯片上的疾病模型，模拟人类的高血压肾病。它由两个通道组成，通道内 lined 有紧密相邻的肾小球内皮细胞和足细胞层，这些细胞经历生理条件下的流体流动，以模拟体内的肾小球微环境。我们的结果表明，肾小球机械力在细胞细胞骨架重排以及导致高血压肾病中观察到的细胞及其连接损伤方面起着至关重要的作用。结果还表明，GC 可以轻松灵活地满足肾脏疾病模型的需求。GC 可以提供药物筛选和毒理学测试，并为肾小球疾病创建潜在的新的个性化和精确治疗平台。
