3D Nephrotoxicity applications & Nortis’ microfluidic organ-on-chip technology

Presented by

Dr. Ed Kelly, Dr. Henning Mann

About this talk

1. The kidney proximal tubule is the primary site of drug-induced nephrotoxicity. I will describe the development of a 3-dimensional flow-directed proximal tubule microphysiological system (MPS). The kidney MPS recapitulates the synthetic, metabolic and transport activities of kidney proximal tubule cells. This MPS is as an ideal platform for ex vivo modeling of nephrotoxicity. Towards this goal, we have evaluated nephrotoxicity in response to challenge with multiple toxicants, including the heavy metal pollutant cadmium, antisense oligonucleotides, the antibiotic polymyxin B and the Chinese herbal product aristolochic acid. We believe that MPS technologies will have major impacts on predictive toxicity testing and human risk assessment. Animal and in vitro systems do not always faithfully recapitulate drug and xenobiotic responses in the clinic or occupational/environmental exposures, respectively. MPS technologies will refine safety assessment and reduce our need for surrogate animal testing. An ultimate goal is to create integrated human MPS organ systems that could replace animal models. 2. Nortis has developed a technology that is used to recapitulate functional units of human organs in microfluidic devices (chips). Such organ models include vasculature, kidney, and liver models for toxicology studies, blood-brain barrier models for drug transport studies, and vascularized tumor microenvironment models for drug efficacy studies.

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