Long-term effects of intrasplenically transplanted adult hepatocytes and fetal liver in hyperbilirubinemic Gunn rats

Abstract

We performed adult hepatocyte transplantation (HCTx) and fetal liver transplantation (FLTx) into the spleens of hyperbilirubinemic Gunn rats in congenic combination and we compared the long‐term effects of these procedures for as long as 12 months. Proliferative activity of intrasplenic hepatocytes was evaluated using antiproliferating cell nuclear antigen (PCNA) immunohistochemical staining. The serum total bilirubin levels (T. Bil) significantly decreased from 7.16 ± 0.25 mg/dl to 4.38 ± 0.60 mg/dl 2 months after HCTx and gradually decreased thereafter until 12 months after transplantation (3.23 ± 0.37 mg/dl, P < 0.05 vs preoperative value). The T. Bil change after FLTx was similar to that of HCTx: 7.22 ± 0.24 mg/dl before FLTx, and 4.92 ± 0.24 and 3.06 ± 0.47 mg/dl, 2 and 12 months after FLTx (P < 0.05), respectively. Bilirubin glucuronides, which were not detectable in the bile from untreated Gunn rats, appeared in considerable amounts 4 months after HCTx and FLTx (27.5% and 36.0% of total bile, respectively). PCNA labeling indices of intrasplenic hepatocytes (4.9%± 0.9% and 3.7%± 0.7%, 6 months after HCTx and FLTx, respectively) were slightly higher than those of normal hepatocytes (1.0%± 0.1%) in the host liver. In conclusion, both adult and fetal rat hepatocytes transplanted into the spleen in congenic combination functioned for at least a year in terms of bilirubin glucuronidation. The spleen is considered to be one of the optimal grafting sites for hepatocytes, with nearly lifelong significant function and proliferative activity.