Beneficial Effects of Immunoisolated Fetal and Neonatal Pig Liver Fragments on Acute Liver Failure in a Large Animal

Abstract

Xenogeneic cell (fragment) transplantation may be used as an interim therapy until the organ allotransplanation. Immunologic rejection, however, constitutes the major hurdle. To overcome this problem, “xeno” fetal and neonatal liver fragments (FLF, NLF) were encapsulated into separate micropore devices that protect them from immunological attack by the recipient. The FLF or NLF were then transplanted into beagles with hepatic failure to observe their biological effects. In Experiment 1 (n = 5) beagles were injected IV with D-galactosamine (D-gal, 1.0 g/kg) on day 0 and then received FLF grafts (0, 0.3, 0.8, 1.0, 2.0 g/kg). In Experiment 2 (n = 6) beagles received NLF grafts (1.8 g/kg) and on the following day were injected with D-gal (1.0 g/kg). In Experiment 1 only the high dose of xeno-FLF (2.0 g/kg) decreased the elevated ALT (GPT) and T. Bil. levels. Histologic examination showed that some of the hepatocytes of the host liver survived only in the high-dose graft. In Experiment 2, at 36 and 48 h after D-gal injection, the transplanted group had a significantly lower AST (GOT) level than the control. The grafted NLF survived for 14 days, according to histologic examinations. Thus, encapsulated FLF and NLF xenotransplantation can prevent liver dysfunction in a large animal hepatic failure model.