Spheroid formation of hepatocytes using synthetic polymer

Masamichi Kamihira, Keisuke Yamada, Ryuji Hamamoto, Shinji Iijima

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


It is known that hepatocytes show the different morphology depending on the surface condition of cultural substratum. The cells form a floating cell-aggregate called spheroid on proteoglycan-coated or positively charged dishes. The liver cell functions are generally high and maintained for the long-term in the spheroid culture. Since spheroid morphology is preferable for the construction of a bioartificial liver, it is important to develop an effective method of preparing spheroids. In this regard, we examined a preparation method of functional spheroid-like cell-aggregates, in which a synthetic polymer, Eudragit was added to culture medium for inducing liver cell-aggregation. The cell-cell attachment of the aggregate was loose at the beginning of the culture, but it became tight and spheroids were formed 2-3 days after inoculation. When 0.1% Eudragit was added to the medium, the liver functions such as albumin secretion, ammonia removal and urea synthesis were enhanced compared with monolayer and conventional spheroid cultures. The spheroid formation was also performed with suspension culture in a spinner flask. Approximately 80% of the cells inoculated formed spheroids by the addition of the polymer. Moreover, the polymer showed a protective effect from cell damage by agitation. Since this procedure does not require surface for cell attachment, a large amount of spheroids can be prepared in suspension culture.

Original languageEnglish
Pages (from-to)398-407
Number of pages10
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - Dec 31 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • History and Philosophy of Science


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