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Considering the importance of the kidney in clearing toxins from the body, implementing nephrotoxicity studies early in the drug development process is crucial. Organ-on-Chip technology promises a predictive test for drug clearance and toxicity in the kidney. An in vitro 3D model of the proximal tubule provides a model of renal secretion that is functionally similar to in vivo tissue in terms of drug metabolism and drug elimination, increasing the translational capacity of a toxicity study.

Other possible applications of our Kidney-on-Chip include drug discovery, pharmacokinetics/pharmacodynamics (PK/PD) studies, and kidney disease models.

Immunofluorescence image of a kidney proximal tubule

A kidney proximal tubule grown in the ParVivo™ microfluidic chip shows an epithelial structure and formation of cilia.

Model features

The ParVivo™ kidney model consists of a perfused human proximal tubule showing similar architecture, morphology, and function as in vivo tissue. Cells undergo shear stresses due to tightly controlled fluid flow as they would in vivo and express the specialized transporter proteins localized to the cell-anatomically location, as shown through immunofluorescence analysis. As a result, the kidney proximal tubule microfluidic chip is a powerful model for drug testing; replicating tubule polarity, transporter expression, secretory and re-absorptive functions, as well as response to toxic insults.

The proximal tubule model is viable for 2-3 weeks depending on the cell source, which can be primary cell sources or from established cell lines.

Polarity markers in the proximal tubule;

A kidney proximal tubule cells show localized expression of key epithelial markers: E-cadherin, P-GP, CD13 on the luminal cell membranes; and NA+K+-ATPase, OCT-2 and OAT-1 at the basolateral cell membranes.

Pre-seeded Proximal Tubule

The ParVivo™ Kidney Chip is available as a preseeded chip , with a ready-to-go proximal tube from primary cells or established cell lines grown in the Nortis’ lab.

Applications

  • Nephrotoxicity
  • Drug discovery
  • PK/PD
  • Kidney disease models

Assays and readout methodologies

  • Transporter studies
  • Clearance studies
  • Permeability studies
  • Viability assessment (imaging/effluent analysis)
  • Injury markers (imaging/effluent analysis)
  • Proteomics

Selected Publications: 

Predicting tubular reabsorption with a human kidney proximal tubule tissue-on-a-chip and physiologically-based modeling. Courtney Sakolish, Zunwei Chen, Chimeddulam Dalaijamts, Kusumica Mitra, Yina Liu, Tracy Fulton, Terry L.Wade, Edward J. Kelly, Ivan Rusyn, Weihsueh A. Chiua. Toxicology in Vitro 63, 2020. doi:10.1016/j.tiv.2019.104752

An Improved Vascularized, Dual-Channel Microphysiological System Facilitates Modeling of Proximal Tubular Solute SecretionAlenka Chapron, Brian D. Chapron, Dale W. Hailey, Shih-Yu Chang, Tomoki Imaoka, Kenneth E. Thummel, Edward Kelly, Jonathan Himmelfarb, Danny Shen, Catherine K. Yeung. ACS Pharmacol. Transl. Sci. 2020. doi:10.1021/acsptsci.9b00078

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