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Abstract: PO2032

Comparative Kidney-on-Chip Toxicity Assessment in Human, Rat, and Dog Kidney Tissue Chips

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Bafti, Sepand, Nortis, Inc., Seattle, Washington, United States
  • Williford, John R., Nortis, Inc., Seattle, Washington, United States
  • Balbiani, Laura Vittoria, Nortis, Inc., Seattle, Washington, United States
Background

The proposed project comprises of the development of a kidney proximal tubule (KPT) microphysiological system (MPS) from human cells as well as two experimental animal species that are typically used in kidney toxicity screening: rat and dog .These KPT-MPS can serve as an important new tool in chemical toxicity screening, allowing cross-referencing animal-based MPS data within vivoanimal data and with human-based MPS data and clinical outcomes. It also has the potential to result in a significant reduction of the use of live animals in studies.

Methods

The Nortis chip is made from silicone in a polycarbonate casing and is designed to use the “mandrel” method for generating channels within a 3D extracellular matrix using retractable small glass fibers. The channels serve as starting points for generating tubular tissue structures, such as vessels or kidney tubules. The chip is compatible with high-quality imaging, tissue sampling, and up- and down-stream fluid collection. Multiple publications have documented the suitability of the Nortis system to generate functional human KPTs and how well they resemble the function of in vivo tubules. All 3D MPS experiments are accompanied by 2D controls for comparison, using a traditional culture dish system. To assess viability of tissue, Live-Dead staining assays were run on canine tubules with Calcein-AM (live) and the nucleic acid stain ethidium homodimer I (dead), the results of which indicated sufficiently viable tubules. Confocal imaging and 3D rendering of these tubules demonstrates presence of key ion and drug transport proteins in their respective basolateral and lumenal domains.

Results

Preliminary studies have shown that rat and canine derived KPT-MPS in the Nortis platform produce structurally viable tissue structures that elicit injury markers in response to nephrotoxic insults using in vivo relevant toxic compounds in a differential manner.

Conclusion

Our preliminary data suggests that Nortis kidney chip allows for an ideal predicitive platfrom for comparative toxicity studies, allowing for fast and highly predictive preclinical simulations.

Funding

  • Other NIH Support