Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function

Prabhas V. Moghe, Francois Berthiaume, Robert M. Ezzell, Mehmet Toner, Ronald G. Tompkins, Martin L. Yarmush

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

Several extracellular matrix (ECM) configurations involving type I collagen and Matrigel were examined for their ability to support differentiated function and polarity of cultured adult rat hepatocytes, Collagen sandwich- and Matrigel-based cultures yielded superior and comparable albumin secretion for at least 2 weeks. In collagen sandwich, hepatocytes were polygonal, and formed multicellular arrays. Collagen sandwich was also found to promote in vivo-like polarization of F-actin, cell adhesion molecules (E-cadherin), and lateral (Na+, K+-ATPase, glucose transporter) and apical (dipeptidyl peptidase, aminopeptidase) membrane polarity markers, but not the expression of the gap junction protein connexin 32 and the epidermal growth factor (EGF) receptor. In contrast, hepatocytes cultured in or on Matrigel were more rounded and formed aggregates. Matrigel-based cultures also elicited detectable levels of connexin and EGF receptor and an altered distribution of F-actin, E-cadherin, and apical and lateral membrane proteins. Composite sandwich configurations containing collagen I and Matrigel restored markers lacking in the collagen sandwich, and showed a variable morphology and membrane polarity. Hepatocyte polarity could thus be manipulated by the overall ECM composition. Furthermore, in composite sandwich cultures, these manipulations can be effected largely independent of changes in hepatocyte morphology and albumin secretion.

Original languageEnglish (US)
Pages (from-to)373-385
Number of pages13
JournalBiomaterials
Volume17
Issue number3
DOIs
StatePublished - Feb 1996

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Collagen sandwich
  • Hepatocyte culture
  • Hepatocyte polarity
  • Matrigel

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