Development of advanced multidimensional in vitro kidney models

The kidney is a complex organ composed mainly of glomerular, tubular, mesangial cells, podocytes, and endothelial cells. The fact that renal cells are terminally differentiated at 34 weeks of gestation is the main obstacle in the regeneration and treatment of acute or chronic renal damage. Considering the annually increasing number of patients with chronic kidney disease, related research aims to improve existing and develop new renal replacement therapy methods. Besides, given the increasing polypharmacy in the ever-ageing population, consideration should be given to developing new drug safety testing methods (e.g., advanced nephrotoxicity models, drug excretion and related interactions). One possible way to address these issues is to isolate and culture renal cells to produce functional in vitro models. The more successful such mimicry is regarding native tissue, the higher is their prediction potential in the systematic investigation of acute and chronic kidney disease's pathophysiology and/or testing of complex drug-related pharmacokinetic aspects. In this proposal, we have chosen such a path. Our project aims to develop 2D and 3D functional in vitro kidney models to study acute and chronic kidney pathophysiology. The developed models will be based on our own isolated kidney cells from kidney (punch-based) biopsy tissue samples of non-cancerous patients. More specifically, the developed in vitro cell models will aim: 1) for excretion observation and nephrotoxicity studies (2D models will focus on the “E part” of the ADME system of non-clinical testing, as well as enable testing of potential drug toxicities towards kidney tissue), 2) to try to recapitulate the complexity of nephron, enabling systematic studies of kidney disease pathologies (3D models will focus on partial and/or full kidney failure). Our research is divided into several work packages, where each chapter represents an upgraded level of complexity of the developed in vitro models in previous chapters. The final step will comprise developing and testing functional 3D bioprinted or spheroid models of kidney failure.