Open AccessMicrophysiological Systems to Assess Nonclinical Toxicity
Author(s) -
Ness Kirk P.,
Chang ShihYu,
Weber Elijah J.,
Zumpano Danielle,
Eaton David L.,
Kelly Edward J.
Publication year - 2017
Publication title -
current protocols in toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.449
H-Index - 23
eISSN - 1934-9262
pISSN - 1934-9254
DOI - 10.1002/cptx.27
Subject(s) - proximal tubule , toxicity , limiting , kidney , drug metabolism , renal tubule , in vitro , transporter , drug , pharmacology , cell culture , biology , medicine , endocrinology , biochemistry , gene , mechanical engineering , genetics , engineering
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. © 2017 by John Wiley & Sons, Inc.