Hepatic organoids for microfluidic drug screening

Lab Chip. 2014 Sep 7;14(17):3290-9. doi: 10.1039/c4lc00531g.

Abstract

We introduce the microfluidic organoids for drug screening (MODS) platform, a digital microfluidic system that is capable of generating arrays of individually addressable, free-floating, three-dimensional hydrogel-based microtissues (or 'organoids'). Here, we focused on liver organoids, driven by the need for early-stage screening methods for hepatotoxicity that enable a "fail early, fail cheaply" strategy in drug discovery. We demonstrate that arrays of hepatic organoids can be formed from co-cultures of HepG2 and NIH-3T3 cells embedded in hydrogel matrices. The organoids exhibit fibroblast-dependent contractile behaviour, and their albumin secretion profiles and cytochrome P450 3A4 activities are better mimics of in vivo liver tissue than comparable two-dimensional cell culture systems. As proof of principle for screening, MODS was used to generate and analyze the effects of a dilution series of acetaminophen on apoptosis and necrosis. With further development, we propose that the MODS platform may be a cost-effective tool in a "fail early, fail cheaply" paradigm of drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hep G2 Cells
  • Humans
  • Liver / chemistry*
  • Liver / drug effects
  • Mice
  • Microfluidic Analytical Techniques / instrumentation*
  • NIH 3T3 Cells
  • Pharmaceutical Preparations / analysis*

Substances

  • Pharmaceutical Preparations