Extracellular matrix (ECM) is a network of proteins and proteoglycans essential for supporting cellular proliferation and physiological behaviour. Particularly, it was shown that kidney basement membrane components (mainly collagen IV and laminin) play a crucial role in the function of different segments of the nephron. An example of this mechanism is hensin, an ECM protein that have shown to promote transition between α and β intercalated cells, stimulating different mechanisms of action in the collecting duct. Current models using organ-on-chip systems mainly use collagen I as scaffold for their systems, without considering segment-specific compositions. Additionally, most kidney models reproduce proximal tubule systems, with no current 3D model of the collecting duct to study physiological mechanisms in vitro. Therefore, the aim of the study is to develop a 3D model of the collecting duct using organ-on-chip system by integrating more physiological and biomimetic ECM components.

M1-CCD cells from collecting duct were cultured on three-lane organ-on-chip systems (OrganoPlate, Mimetas) to produce tubular structures, where the middle channel was filled with a permeable ECM formed by a mix of Collagen I, Laminin I and Collagen IV and the top channel was filled with M1-CCD.

Preliminary results of the culture of M1-CCD on low-attachment plates to verify the intrinsic ability of cells to form 3D structures, confirmed that they are able to rearrange in round 3D organizations. Next steps include culture of M1-CCD on the OrganoPlate system including different combinations of basement membrane proteins such as collagen IV and laminin to the recommended collagen I, in order to create a more biomimetic environment for collecting duct epithelial cells. The goal of the study will be to eventually incorporate patient urine-derived cells from the collecting duct to create a more accurate and personalised platform for disease modelling.