Progress in researches on in vitro alternative model for nephrotoxicity evaluation

Abstract

With the introduction of Toxicity Testing in the 21st Century: A Vision and Strategy, the focus of toxicity testing has shifted from animal experiments to in vitro models using human resource cells or cellular components. As kidney is a major target for drug-induced toxicity and the drug-induced toxicity remains a major problem in developing new drugs, a predictive in vitro model is urgently needed to evaluate the renal toxicity of exogenous compounds. However, current in vitro cellular models poorly replicate both the morphology and the function of kidney tubules and therefore fail to demonstrate injury responses to that would be nephrotoxic in vivo. The resource and characteristics of cellular models, cell culture conditions, and readouts of injury are important in establishing an in vitro model. The development of differentiation of pluripotent stem cells into multiple renal cell types, 3 dimensional culture systems and kidney-on-a-chip technology, omics technology and high-content screening have opened a range of potential new platforms for evaluating compounds nephrotoxicity and promoted in vitro to in vivo extrapolation. This study summarizes the latest advances in in vitro nephrotoxicity assessment models.