Modeling the kidney with human pluripotent cells: Applications for toxicology and organ repair

Acute kidney damage and dysfunction is a significant medical problem that is brought about by disease or by drug-induced toxicity. Though this problem has long been recognized, our understanding of human kidney damage has relied heavily upon the use of animal models and the study of human kidneys after damage has already occurred. Recent advances in the field of stem cell research now make it possible to investigate the dynamic mechanisms of damage that occur in the kidneyin human renal cells derived from human pluripotent stem cells (hPSCs). In this review, we briefly summarize normal human kidney development and describe how this knowledge has been used to inform strategies for the directed differentiation of hPSCs to renal cell types and kidney organoids. We also review recent translational advances in the use of such platforms to investigate molecular and cellular mechanisms of nephrotoxicity and elucidation of modes of action of drug-induced kidney toxicity as mediated by specific drugs of concern. Finally, we discuss the prospects for the use of cell-based therapeutics to reverse extant kidney damage in vivo, and eventually, the goal of restoration of renal function with stem-cell-derived organs.