HEPATOCYTE TRANSPLANTATION - AN ALTERNATIVE SYSTEM FOR EVALUATING CELL-SURVIVAL AND IMMUNOISOLATION

To evaluate systems for barrier immunoisolation of transplanted hepato cytes, we used transgenic mouse hepatocytes that secrete HBsAg. Hepato cytes were rapidly encapsulated in chitosan, a cationic polymer derive d by deacetylation of chitin. Chitosan was allowed to electrostaticall y bond with anionic sodium alginate for creating an outer bipolymer me mbrane of the capsules. After encapsulation, hepatocyte viability rema ined unchanged for seven days in vitro with secretion of HBsAg into th e culture medium throughout this period. Following intraperitoneal tra nsplantation of encapsulated hepatocytes, HBsAg promptly appeared in b lood of recipients. In congeneic recipients, serum HBsAg peaked at two weeks. Hepatocytes were present in recovered chitosan capsules and ex pressed HBsAg mRNA. In allogeneic recipients, however, serum HBsAg dis appeared within one week and recovered chitosan capsules showed lympho mononuclear cells but not hepatocytes. Transplantation of chitosan enc apsulatd HbsAg secreting hepatocytes failed to induce an anti-HBs resp onse, suggesting modulation of the host immune response. These results indicate that transplantation systems using genetically modified hepa tocytes which secrete gene products in the blood of recipients should facilitate evaluation of hepatocyte encapsulation.