Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration

Biotechnol Prog. 1991 May-Jun;7(3):237-45. doi: 10.1021/bp00009a007.


In an effort to reconstruct the cellular polarity normally found in the liver, adult rat hepatocytes were sandwiched between two layers of hydrated rat tail tendon collagen matrix. Functionally, sandwiched hepatocytes maintained the secretion of albumin, transferrin, fibrinogen, bile acids, and urea for at least 6 weeks, whereas cells cultured on a single layer of collagen gel ceased such secretion in 1-2 weeks. After 1 week of culture on a single layer of collagen gel, hepatocytes could still recover these lost functions when a second layer of collagen gel was applied. The exact nature of the substrate for constructing the sandwich system appeared to be unimportant as long as it allowed cellular attachment. Hepatocytes cultured in the sandwich system appeared to maintain a distribution of actin filaments similar to the in vivo state, whereas cells cultured on a single layer of collagen gel showed abnormal formation of stress fibers. These studies suggest that simple manipulations of the configuration of extracellular elements can dramatically alter the behavior of cultured hepatocytes.

Publication types

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

MeSH terms

  • Actins / analysis
  • Animals
  • Bile Acids and Salts / biosynthesis
  • Cells, Cultured
  • Collagen*
  • Culture Media
  • Female
  • Inactivation, Metabolic
  • Liver / cytology
  • Liver / metabolism*
  • Proteins / metabolism
  • Rats
  • Rats, Inbred Lew
  • Tendons / chemistry
  • Time Factors
  • Urea / metabolism


  • Actins
  • Bile Acids and Salts
  • Culture Media
  • Proteins
  • Urea
  • Collagen