The kidney plays a crucial role in drug development, as it dictates drug clearance and is a target for drug-induced toxicity. Nephrotoxicity of candidate drugs is one of the major reasons for drug attrition during preclinical, clinical and post-approval stages of drug development. These failures during the final stages of the drug development process are partially caused by the use of inaccurate preclinical nephrotoxicity models. Therefore, an accurate kidney model for Multi-Organ-Chip applications could revolutionize drug trials by providing a relevant in vitro platform.
In this study, we generate an autologous kidney-on-a-chip that encompasses a glomerular and a tubular model. Induced pluripotent stem (iPS) cell-derived podocytes and tubular cells are seeded into the HUMIMIC Chip4, which enables the long-term co-cultivation of the renal model with up to three additional organ equivalents with a defined fluid flow and shear stress. The final maturation of the iPS cell-derived podocytes and tubular cells occurs within the Multi-Organ-Chip. After the renal cells’ final maturation, the co-culture can be maintained for at least 14 days.
The kidney-on-a-chip exhibits a stable metabolism, a cellular barrier that prevents albumin from entering the excretory circuit, and the cells demonstrate a steady expression of key podocyte and tubular markers.
The kidney-on-a-chip can be employed for elaborate safety, efficacy and nephrotoxicity studies, as wells as for mechanistic studies of renal development or disease. The combination of the renal model with other organ equivalents further enables systemic studies, including ADME experiments. Therefore, the kidney-on-a-chip presents a human and systemic alternative to current in vivo and in vitro models.