Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy
| Autor: | Jing Wang, Weidong Wang, Wen Xinyu, Hongli Lin, Mengying Zhou, Taihua Wu, Mingzhou Yang, Ming Fang, Bingcheng Lin, Zhang Xulang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Hypertension Renal Kidney Glomerulus Disease In Vitro Techniques Kidney urologic and male genital diseases Article Diabetic nephropathy 03 medical and health sciences In vivo Lab-On-A-Chip Devices Rats Inbred SHR Hypertensive Nephropathy Cell Adhesion medicine Animals Humans Glomerular disease Glomerular diseases Cytoskeleton Nephritis Multidisciplinary Podocytes urogenital system business.industry Glomerulosclerosis medicine.disease Actins Coculture Techniques female genital diseases and pregnancy complications Rats 030104 developmental biology Immunoglobulin G Hypertension Kidney Failure Chronic Kidney Diseases beta 2-Microglobulin business |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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