Enhanced cell aggregation and liver functions using polymers modified with a cell-specific ligand in primary hepatocyte cultures

Keisuke Yamada, Masamichi Kamihira, Shinji Iijima

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Hepatocytes cultured as multicellular aggregates called spheroids exhibit enhanced liver functions and maintain them over a long period compared with monolayer culture. We previously reported the induction of hepatocyte spheroids using the synthetic polymer Eudragit (a copolymer of methacrylic acid and methyl-methacrylate) as an artificial matrix in a cell suspension system. In this method, hepatocyte aggregation was promoted by the effects of electrostatic and hydrophobic interactions between cells and the polymer. To enhance the cell aggregation ability and cell-specificity of the polymer, in the present study, we prepared hepatocyte-targeting polymers containing lactone, a ligand of the asialoglycoprotein receptor. Addition of the lactone-modified polymers to the medium promoted cell aggregation and spheroid formation more effectively than unmodified Endragit. The spheroids induced by the polymers exhibited enhanced liver functions, i.e., albumin secretion, ammonia removal, and urea synthesis, from early in the culture. We also investigated the induction of hetero-spheroids composed of various liver constitutive cells by this method. The hetero-spheroids induced by the polymers showed improved liver functions.

Original languageEnglish
Pages (from-to)557-562
Number of pages6
JournalJournal of Bioscience and Bioengineering
Issue number5
Publication statusPublished - Jan 1 1999


All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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