TY - JOUR KW - cross-talk study KW - glomerulus-on-a-chip KW - mesangium KW - tri-culture model AU - Ramin Pajoumshariati AU - Lorna Ewart AU - Ville Kujala AU - Raymond Luc AU - Samantha Peel AU - Adam Corrigan AU - Heather Weber AU - Bramasta Nugraha AU - Pernille B. L. Hansen AU - Julie Williams AB - The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment. BT - Advanced Science (Weinheim, Baden-Wurttemberg, Germany) DA - 2023-10-22 DO - 10.1002/advs.202303131 LA - eng N2 - The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment. PY - 2023 EP - e2303131 T2 - Advanced Science (Weinheim, Baden-Wurttemberg, Germany) TI - Physiological Replication of the Human Glomerulus Using a Triple Culture Microphysiological System SN - 2198-3844 ER -