Hepatocyte transplantation: An alternative system for evaluating cell survival and immunoisolation

S. Gupta, S. K. Kim, R. P. Vemuru, E. Aragona, P. R. Yernemi, R. D. Burk, C. K. Rha

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

To evaluate systems for barrier immunoisolation of transplanted hepatocytes, we used transgenic mouse hepatocytes that secrete HBsAg. Hepatocytes were rapidly encapsulated in chitosan, a cationic polymer derived by deacetylation of chitin. Chitosan was allowed to electrostatically bond with anionic sodium alginate for creating an outer bipolymer membrane of the capsules. After encapsulation, hepatocyte viability remained unchanged for seven days in vitro with secretion of HBsAg into the culture medium throughout this period. Following intraperitoneal transplantation of encapsulated hepatocytes, HBsAg promptly appeared in blood of recipients. In congeneic recipients, serum HBsAg peaked at two weeks. Hepatocytes were present in recovered chitosan capsules and expressed HBsAg mRNA. In allogeneic recipients, however, serum HBsAg disappeared within one week and recovered chitosan capsules showed lymphomononuclear cells but not hepatocytes. Transplantation of chitosan encapsulatd HbsAg secreting hepatocytes failed to induce an anti-HBs response, suggesting modulation of the host immune response. These results indicate that transplantation systems using genetically modified hepatocytes which secrete gene products in the blood of recipients should facilitate evaluation of hepatocyte encapsulation.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalInternational Journal of Artificial Organs
Volume16
Issue number3
StatePublished - Jan 1 1993

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Keywords

  • bioartificial liver
  • hepatitis B virus
  • hepatocyte transplantation
  • immobilized cells
  • transgenic mouse

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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