Growth factors and nonparenchymal cell conditioned media induce mitogenic responses in stable long-term adult rat hepatocyte cultures

Yoon H. Kang, François Berthiaume, Bharath D. Nath, Martin L. Yarmush

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Most prior studies have characterized hepatocyte proliferative responses in culture systems that do not express a stable differentiated phenotype. We investigated the DNA synthetic response of long-term stable hepatocyte cultures to growth factor stimulation as well as conditioning with nonparenchymal cells (NPCs). Primary rat hepatocytes were cultured on a single layer of collagen (h/C) or Matrigel (h/M), or in a collagen sandwich (C/h/C) or collagen-Matrigel sandwich (M/h/C). Hepatocytes were cultured for 7 days to allow phenotypic stabilization before growth factor addition, except for h/C cultures, which are unstable, where growth factors were added 1 day after seeding. Culture medium was supplemented with a mixture of hepatocyte, epidermal, and vascular endothelial growth factors and interleukin-6, either directly or after conditioning with NPCs for 24 h. Growth factors alone induced hepatocyte DNA synthesis, as measured via [3H]thymidine uptake, in the h/C, C/h/C, and M/h/C configurations. h/M exhibited very low levels of DNA synthesis. In the C/h/C and M/h/C configurations, the greatest stimulation was obtained using NPC-conditioned growth factors. This response was sustained for several days and without decreasing albumin or urea synthesis. These results suggest that hepatocyte mitogens and NPC-derived factors can stimulate DNA synthesis in stable and differentiated hepatocyte cultures.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalExperimental cell research
Volume293
Issue number2
DOIs
StatePublished - Feb 15 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Cell cycle
  • Cytokines
  • Growth factors
  • Hepatocyte
  • Liver regeneration
  • Nonparenchymal cells

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