A novel modular bioreactor to in vitro study the hepatic sinusoid

PLoS One. 2014 Nov 6;9(11):e111864. doi: 10.1371/journal.pone.0111864. eCollection 2014.


We describe a unique, versatile bioreactor consisting of two plates and a modified commercial porous membrane suitable for in vitro analysis of the liver sinusoid. The modular bioreactor allows i) excellent control of the cell seeding process; ii) cell culture under controlled shear stress stimulus, and; iii) individual analysis of each cell type upon completion of the experiment. The advantages of the bioreactor detailed here are derived from the modification of a commercial porous membrane with an elastomeric wall specifically moulded in order to define the cell culture area, to act as a gasket that will fit into the bioreactor, and to provide improved mechanical robustness. The device presented herein has been designed to simulate the in vivo organization of a liver sinusoid and tested by co-culturing endothelial cells (EC) and hepatic stellate cells (HSC). The results show both an optimal morphology of the endothelial cells as well as an improvement in the phenotype of stellate cells, most probably due to paracrine factors released from endothelial cells. This device is proposed as a versatile, easy-to-use co-culture system that can be applied to biomedical research of vascular systems, including the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bioreactors
  • Coculture Techniques / instrumentation*
  • Coculture Techniques / methods*
  • Endothelial Cells / metabolism*
  • Hepatic Stellate Cells / metabolism*
  • Humans
  • Stress, Mechanical
  • Umbilical Veins / cytology

Grant support

This work was supported by: CSIC (PIE 201450E116) (RV); Instituto de Salud Carlos III (FIS PI11/00235) (JGS); Ministerio de Economía y Competitividad (SAF2012-31238) (CP); European Union (Fondos FEDER, “una manera de hacer Europa”) (JGS and CP); European Community's Seventh Framework Programme (EC FP7/2007-2013, grant agreement 229673) (JGS); CIBER-EHD (funded by Instituto de Salud Carlos III) (JGS and CP); and CIBER-BBN (funded by Instituto de Salud Carlos III) (RV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.