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Unraveling the complex behavior of healthy and diseased podocytes by analyzing the changes in their unique arrangement of foot processes, slit diaphragm, and three-dimensional (3D) morphology is a long-standing goal in kidney-glomerular research. The complexities surrounding podocyte accessibility in animal models and growing evidence of differences between human and animal systems have compelled researchers to look for alternate approaches to study human podocyte behaviors. Current models in the field use kidney organoids or podocytes cultured on a filter surface in a microfluidic setup to understand their behavior in various conditions. Podocytes in these platforms have some functionality; however, they do not recapitulate the in vivo-like arrangement of podocytes with vessels, lack kidney-relevant natural extracellular matrix (ECM) guidance, and include non-biological filters between endothelial cells and podocytes. In our approach, we propose a novel system in which we expect to recapitulate the unique arrangement of in vivo podocytes. This system is a major innovation in the glomerular research field, as it allows podocytes to attach and spread over the outer curvature of a perfused vessel without any filter placed between them, thus mimicking the in vivo glomerular arrangement and enabling podocytes to behave similarly to invivo. The overriding impact of this system is that it will fill a current void in the glomerular disease research field and afford a system that can function for molecular, cellular, and tissue-level experimentation of podocytes in an invivo-like arrangement. The fact that this system is invitro in nature and uses podocytes and endothelial cells derived from common IPSC cells (same genetic makeup) makes it optimal for human podocyte research. Thus, the potential impact is immeasurable. For example, one of the areas where it could have an immediate impact is Drug Discovery: There are no relevant drug tools available to test new therapeutics for podocyte diseases. The systems we develop can be tailored into a relevant drug screening tool for various glomerular diseases. Furthermore, the approach can catalyze innovation in synthetic kidney research. Mechanisms: The system can be a tool to perturb and test mutant proteins' effects or assess modifiers' role (flow stress, high glucose, or other factors) in podocytes.
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