Disease models

A high throughput cell co-culture system could be used to screen therapies for HBV infection. The system utilizes a microwell plate for simultaneously generating up to 96 co-cultures of pooled primary human hepatocytes derived from multiple individuals and a non-parenchymal mouse embryonic fibroblast (MEF) stromal cell line to promote the formation of bile canaliculi morphology, then infecting the co-cultures with HBV for up to 30 days -- about 11 days longer than conventional HBV infection models allow. In a proof-of-concept experiment, pre-infection treatment of the co-cultures with a peptide inhibitor of viral entry decreased HBV infectivity compared with a control peptide. In HBC-infected co-cultures, the viral DNA polymerase inhibitor Baraclude entecavir decreased viral levels in a dose-dependent manner. Next steps in collaboration with Hurel Corp. include optimizing the system for higher throughput, utilizing it to screen compounds for chronic HBV therapies, and adapting it to model additional viral and parasitic liver infections...