Related Experiment Video
Updated: Mar 15, 2026
Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells
Published on: November 4, 2022
Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy
Mengying Zhou1, Xulang Zhang2, Xinyu Wen1
1Department 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.
Insights
Glomerular hypertension drives kidney disease. A new glomerulus-on-a-chip model reveals how mechanical forces cause cell damage and leakage, offering insights for treating hypertensive nephropathy.
Area of Science:
- Nephrology
- Biomedical Engineering
- Microfluidics
Background:
- Glomerular hypertension accelerates kidney disease progression to end-stage renal disease.
- Glomerular sclerosis, common in hypertensive and diabetic nephropathy, is poorly understood due to limited disease models.
- Existing models lack the ability to replicate complex mechanical forces and organ-level disease processes.
Purpose of the Study:
- To develop a novel in vitro model for studying glomerular hypertension and its effects on the glomerulus.
- To investigate the precise mechanisms by which glomerular hypertension induces glomerular sclerosis.
- To establish a platform for drug screening and therapeutic development for glomerular diseases.
Main Methods:
- Development of a "glomerulus-on-a-chip" (GC) microfluidic device.
- Reconstitution of the glomerulus with endothelial cells and podocytes in a two-channel system.
- Application of physiological fluid flow to mimic in vivo glomerular microenvironment and mechanical forces.
Main Results:
- The GC model successfully mimicked human hypertensive nephropathy.
- Glomerular mechanical forces were shown to be critical in cytoskeletal rearrangement and cell junction damage.
- The device demonstrated increased glomerular leakage, consistent with hypertensive nephropathy.
Conclusions:
- The glomerulus-on-a-chip is a viable model for studying hypertensive nephropathy.
- Mechanical forces play a significant role in the pathogenesis of glomerular sclerosis.
- The GC platform offers potential for drug screening, toxicology testing, and personalized therapies for glomerular diseases.
Abstract:
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.
