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<p>The integrity of the glomerular filtration barrier is essential for kidney function, with glomerular endothelial cells and podocytes playing critical roles. However, traditional <i>in vitro</i> models, which typically rely on mouse-derived cells, are limited in replicating the complex crosstalk between these cells, hindering progress in kidney research and dialysis treatment. To address this gap, we developed a glomerulus-on-a-chip model using human glomerular endothelial cells and podocytes co-cultured within a microfluidic system. Using this model, we investigated how the co-culture of glomerular endothelial cells and podocytes influences the structural features and cellular organization of the filtration barrier. The chip featured two parallel microfluidic channels separated by a polyethylene terephthalate (PET) membrane. The system was optimized to support the formation of a humanized glomerular basement membrane (GBM). In our glomerulus-on-a-chip model, glomerular endothelial cells and podocytes were cultured on opposite sides of the membrane, utilizing a collagen I coating derived from rat tail. Structural barrier organization was notably enhanced when glomerular endothelial cells were co-cultured with podocytes, compared to when either cell type was cultured alone. We employed confocal microscopy and cell trackers to monitor cell morphology and interactions. Both qualitative and quantitative analyses revealed significant improvements in structural organization and cellular alignment. We introduce an innovative glomerulus-on-a-chip co-culture model and, for the first time, demonstrate that co-culturing glomerular endothelial cells with podocytes influences their morphology within the model. Additionally, we show that co-culturing both cell types leads to the formation of a GBM with well-defined structural characteristics. The optimal ratio of glomerular endothelial cells to podocytes was determined to be 1:1, ensuring a structurally organized representation of the glomerular interface. This model provides a promising platform for advancing our understanding of kidney filtration and serves as a valuable tool for developing dialysis membranes.</p>

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Establishment of a humanized glomerular basement membrane on a dual-channel microfluidic chip using co-cultured human renal endothelial cells and podocytes

  • 期刊论文

  • 发表日期：

    2026年4月13日

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  • Marwa Al Hassan,
  • Jumanah Bahig,
  • Katalin Szaszi,
  • Huu Doan,
  • Ahmed Shoker,
  • Amira Abdelrasoul

摘要

The integrity of the glomerular filtration barrier is essential for kidney function, with glomerular endothelial cells and podocytes playing critical roles. However, traditional in vitro models, which typically rely on mouse-derived cells, are limited in replicating the complex crosstalk between these cells, hindering progress in kidney research and dialysis treatment. To address this gap, we developed a glomerulus-on-a-chip model using human glomerular endothelial cells and podocytes co-cultured within a microfluidic system. Using this model, we investigated how the co-culture of glomerular endothelial cells and podocytes influences the structural features and cellular organization of the filtration barrier. The chip featured two parallel microfluidic channels separated by a polyethylene terephthalate (PET) membrane. The system was optimized to support the formation of a humanized glomerular basement membrane (GBM). In our glomerulus-on-a-chip model, glomerular endothelial cells and podocytes were cultured on opposite sides of the membrane, utilizing a collagen I coating derived from rat tail. Structural barrier organization was notably enhanced when glomerular endothelial cells were co-cultured with podocytes, compared to when either cell type was cultured alone. We employed confocal microscopy and cell trackers to monitor cell morphology and interactions. Both qualitative and quantitative analyses revealed significant improvements in structural organization and cellular alignment. We introduce an innovative glomerulus-on-a-chip co-culture model and, for the first time, demonstrate that co-culturing glomerular endothelial cells with podocytes influences their morphology within the model. Additionally, we show that co-culturing both cell types leads to the formation of a GBM with well-defined structural characteristics. The optimal ratio of glomerular endothelial cells to podocytes was determined to be 1:1, ensuring a structurally organized representation of the glomerular interface. This model provides a promising platform for advancing our understanding of kidney filtration and serves as a valuable tool for developing dialysis membranes.