Microphysiological Systems to Assess Nonclinical Toxicity.

Van Ness KP1, Chang SY2, Weber EJ1, Zumpano D3, Eaton DL2, Kelly EJ1
Source: Curr Protoc Immunol
Publication Date: ()
Issue: 14: 1-14
Cells used in publication:
Hepatocyte, human
Species: human
Tissue Origin: liver


The liver and the kidney are key toxicity target organs during drug development campaigns, as they typically carry the burden of drug transport and metabolism. Primary hepatocytes and proximal tubule epithelial cells grown in traditional in vitro 2-D culture systems do not maintain transporter and metabolic functions, thus limiting their utility for nonclinical toxicology investigations. We have developed a renal and hepatic microphysiological system (MPS) platform that uses a commercially available MPS device as the core cell culture platform for our methodologies. We describe protocols for isolating and propagating human proximal epithelial cells and how to seed and culture a renal MPS to recapitulate the human proximal tubule. We present two methods to culture hepatocytes within an MPS and the steps required to connect a renal MPS to a liver MPS