Profiling the Impact of Medium Formulation on Morphology and Functionality of Primary Hepatocytes in vitro

Leonard J Nelson, Philipp Treskes, A Forbes Howie, Simon W Walker, Peter C Hayes, John N Plevris

Research output: Contribution to journalArticlepeer-review

Abstract

The characterization of fully-defined in vitro hepatic culture systems requires testing of functional and morphological variables to obtain the optimal trophic support, particularly for cell therapeutics including bioartificial liver systems (BALs). Using serum-free fully-defined culture medium formulations, we measured synthetic, detoxification and metabolic variables of primary porcine hepatocytes (PPHs) - integrated these datasets using a defined scoring system and correlated this hepatocyte biological activity index (HBAI) with morphological parameters. Hepatic-specific functions exceeded those of both primary human hepatocytes (PHHs) and HepaRG cells, whilst retaining biotransformation potential and in vivo-like ultrastructural morphology, suggesting PPHs as a potential surrogate for PHHs in various biotech applications. The HBAI permits assessment of global functional capacity allowing the rational choice of optimal trophic support for a defined operational task (including BALs, hepatocellular transplantation, and cytochrome P450 (CYP450) drug metabolism studies), mitigates risk associated with sub-optimal culture systems, and reduces time and cost of research and therapeutic applications.
Original languageEnglish
Article number2735
JournalScientific Reports
Volume3
DOIs
Publication statusPublished - 24 Sep 2013

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