Long-term maintenance of a microfluidic 3D human liver sinusoid

Biotechnol Bioeng. 2016 Jan;113(1):241-6. doi: 10.1002/bit.25700. Epub 2015 Aug 26.

Abstract

The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies.

Keywords: 3D microtissue; hepatocytes; liver sinusoid; liver-on-a-chip; microfludics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Drug Evaluation, Preclinical / methods
  • Humans
  • Liver / physiology*
  • Microfluidics / methods*
  • Models, Biological
  • Organ Culture Techniques / methods*
  • Time Factors