Abstract

The Use of Organotypic Liver Co-cultures for Use in Disease Modeling and Drug Development

Kenneth Brouwer, Vice President – Technology, ADME-TOX, BioIVT

As the discovery and development of anti-fibrotic therapies still rely heavily on animal models, there remains an opportunity for robust and relevant in vitro models to support the identification and preclinical evaluation of potential new anti-fibrotic drugs. To this end, BioIVT has developed and characterized several human liver models which help to answer these questions.  The HEPATOPAC^® micropatterned hepatocyte co-culture and the 3D ORGANDOT^TM systems allow for the investigation of questions with increasing complexity and experimental duration.  In each case the incorporation of liver non-parenchymal fractions and extended culture time allow for better prediction of drug metabolism and disposition as well as disease model related endpoints.  For the ORGANDOT system, the inclusion of both Kupffer and stellate cells support the fibrotic phenotypic changes induced with TGFß1 treatment providing an in vitro model for anti-fibrotic drug efficacy.  We will report on data which demonstrates the broad utility in adding cellular and structural complexity to hepatocyte cultures as well as the optimization of endpoints including, molecular and immunohistochemical markers for the study of anti-fibrotic therapies.