Abstract
AIM: To investigate the influence of immune tolerance induced by intrauterine exposure to fetal hepatocytes on liver transplantation in the adult rat. METHODS: LOU/CN rat fetal hepatocytes were injected into the fetuses of pregnant CHN rats (14-16 days of gestation). At 7-9 weeks of age, the surviving male rats received orthotopic liver transplantation (OLT) from male LOU/CN donors and the survival period was observed and monitered by mixed lymphocyte reaction assay and cytotoxicity test. RESULTS: (1) A total of 31 pregnant CHN rats with 172 fetuses received fetal hepatocytes from LOU/CN rats via intrauterine injection. Among them, thirteen pregnant rats showed normal parturition, with 74 neonatal rats growing up normally. (2) The mean survival period after OLT in rats with fetal exposure to fetal hepatocytes was 32.1+/-3.7 days, which was significantly different from the control (11.8+/-2.3 days, P<0.01) in rats without fetal induction of immune tolerance. (3) Mixed lymphocyte proliferation assays yielded remarkable discrepancies between the groups of rats with- or without fetal exposure to fetal hepatocytes, with values of 8,411+/-1,361 and 22,473+/-1,856 (CPM+/-SD, P<0.01) respectively. (4) Cytotoxicity assays showed values of 21.2+/-6.5 % and 64.5+/-7.2 % (P<0.01) in adult rats with or without fetal induction of immune tolerance. CONCLUSION: Intrauterine injection of fetal hepatocytes into rat fetuses can prolong the survival period of liver transplant adult male rats recipients, inducting immune tolerance in OLT.