06 Aug Microfluidic kidney chip for detection of drug-induced toxicity
A major challenge in drug development pipeline lies in avoiding organ-specific toxicity. Microfluidic in vitro models for drug toxicity screening such as organ on chips can play an important role in this sense by providing robust methods for evaluating cellular responses in a controllable microenvironment. For this week’s research highlight, we have selected a microfluidic kidney model reported in Scientific Reports that explores a commonly reported drug-induced complication in the proximal tubule (PT) by taking advantage of integrated sensors for measuring transepithelial electrical resistance (TEER).
“In this paper, we explore the ability to detect drug-induced kidney toxicity in primary PT cells using TEER sensing in a high-throughput model, while screening the effects of two flow conditions and microvascular co-culture. PREDICT96 is a high-throughput microfluidic system with rapid TEER measurement capability that enables parallel culture of 96 independent tissue replicates and control of multiple fluid flows within an industry-standard well-plate footprint“, the authors explained.
“We demonstrated that TEER was an informative metric of cisplatin toxicity for hRPTEC-hMVEC co-cultures but not for hRPTEC in mono-culture. Changes in co-culture TEER correlated with hRPTEC tight junction expression and aligned with trends demonstrated by a standard cytotoxicity assay. Notably, TEER sensing revealed a decrease in co-culture barrier function due to cisplatin that occurred prior to significant increases in cell death.”, the authors explained.
Figures and the abstract are reproduced from Shaughnessey, E.M., Kann, S.H., Azizgolshani, H. et al. Evaluation of rapid transepithelial electrical resistance (TEER) measurement as a metric of kidney toxicity in a high-throughput microfluidic culture system. Sci Rep 12, 13182 (2022). https://doi.org/10.1038/s41598-022-16590-9