Modular, pumpless body-on-a-chip platform for the co-culture of GI tract epithelium and 3D primary liver tissue

Lab Chip. 2016 Jul 5;16(14):2719-29. doi: 10.1039/c6lc00461j.

Abstract

We have developed an expandable modular body-on-a-chip system that allows for a plug-and-play approach with several in vitro tissues. The design consists of single-organ chips that are combined with each other to yield a multi-organ body-on-a-chip system. Fluidic flow through the organ chips is driven via gravity and controlled passively via hydraulic resistances of the microfluidic channel network. Such pumpless body-on-a-chip devices are inexpensive and easy to use. We tested the device by culturing GI tract tissue and liver tissue within the device. Integrated Ag/AgCl electrodes were used to measure the resistance across the GI tract cell layer. The transepithelial resistance (TEER) reached values between 250 to 650 Ω cm(2) throughout the 14 day co-culture period. These data indicate that the GI tract cells retained their viability and the GI tract layer as a whole retained its barrier function. Throughout the 14 day co-culture period we measured low amounts of aspartate aminotransferase (AST, ∼10-17.5 U L(-1)), indicating low rates of liver cell death. Metabolic rates of hepatocytes were comparable to those of hepatocytes in single-organ fluidic cell culture systems (albumin production ranged between 3-6 μg per day per million hepatocytes and urea production ranged between 150-200 μg per day per million hepatocytes). Induced CYP activities were higher than previously measured with microfluidic liver only systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Albumins / metabolism
  • Aspartate Aminotransferases / metabolism
  • Caco-2 Cells
  • Cell Death
  • Coculture Techniques / instrumentation*
  • Coculture Techniques / methods*
  • Cytochrome P-450 CYP1A1 / metabolism
  • Electrodes
  • Epithelium / metabolism
  • Equipment Design / instrumentation
  • Equipment Design / methods
  • Gastrointestinal Tract / cytology*
  • Hepatocytes / cytology
  • Humans
  • Lab-On-A-Chip Devices
  • Liver / cytology*
  • Organ Culture Techniques / instrumentation
  • Organ Culture Techniques / methods
  • Urea / metabolism

Substances

  • Albumins
  • Urea
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • Aspartate Aminotransferases