Conference Report

Digestive Diseases and Sciences

, Volume 36, Issue 4, pp 489-493

First online:

Mechanisms controlling growth of hepatocytes in primary culture

  • Akira IchiharaAffiliated withInstitute for Enzyme Research, University of Tokushima

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Mature hepatocytes in primary culture express most of the functions and hormonal responsiveness seen in normal liver studiedin vivo. The growth of hepatocytes in culture is regulated by various growth factors. We have identified a hepatocyte growth factor that is isolated from rat platelets. We found that rat platelets also contain a growth inhibitor, transforming growth factor-β which is secreted as a latent molecule. Its latency is due to its binding with a masking protein. Growth of hepatocytes is also suppressed by interleukin-1 (IL-1) and IL-6. Moreover, the growth and functions of liver cells in culture are regulated reciprocally by cell density: at higher cell density liver-specific functions are expressed and growth is suppressed, whereas the opposite situation is observed at lower cell density. In contrast, neonatal hepatocytes in culture grow autonomously without a requirement for added hormones. This autonomous growth is due to an autocrine mechanism in which the cells secrete one or more growth factors into the culture medium. However, this autonomous growth ceases one week after birth at a time when the cells begin to express differentiated characteristics. Based upon these data, the mechanisms of liver regeneration, differentiation, and hepatocarcinogenesis are discussed.

Key Words

hepatocyte growth primary culture hepatocarcinogenesis growth factor