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Physiological Replication of the Human Glomerulus Using a Triple Culture Microphysiological System.
Ramin Pajoumshariati1, Lorna Ewart2, Ville Kujala2
1Bioscience Renal, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, 431 83, Sweden.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 22, 2023
Summary
This study introduces a new microphysiological system for studying the glomerulus, including mesangial cells. This advanced in vitro model improves understanding of kidney disease and glomerular biology.
Area of Science:
- Nephrology
- Cell Biology
- Biomedical Engineering
Background:
- Glomerular function relies on intricate cell-cell and matrix interactions.
- Existing in vitro models often lack key cell types, such as mesangial cells, and their 3D matrix context.
- Replicating glomerular complexity in vitro is crucial for advancing biological understanding in health and disease.
Purpose of the Study:
- To develop a novel microphysiological system that accurately recapitulates the anatomical and cellular complexity of the glomerulus.
- To investigate the role of all resident renal cell types, including mesangial cells, in a 3D matrix.
- To provide a more translatable in vitro model for studying glomerular biology.
Main Methods:
- Development of a microphysiological system incorporating all resident renal cell types.
- Detailed transcriptomic analysis to characterize the biology of each cell type within the system.
- Functional assessment of albumin retention to validate the model's physiological relevance.
Main Results:
- The developed system successfully includes all resident renal cell types in an anatomically relevant manner.
- Transcriptomic analysis revealed the specific biological contributions of each cell type.
- The model demonstrated functionally appropriate albumin retention, confirming its physiological relevance.
- Mesangial cells were identified as crucial for promoting the health and maturity of other glomerular cell types.
- Comparison with 2D cultures indicated that glomerular cells in simple 2D culture exhibit a phenotype more reflective of human disease dysfunction.
Conclusions:
- The novel microphysiological system offers a more accurate and translatable platform for studying glomerular biology.
- The inclusion of mesangial cells in a 3D matrix is vital for mimicking in vivo glomerular function and health.
- This model enhances the capability to investigate kidney disease mechanisms and test potential therapeutics.
