LONG-TERM EFFECTS OF INTRASPLENICALLY TRANSPLANTED ADULT HEPATOCYTES AND FETAL LIVER IN HYPERBILIRUBINEMIC GUNN-RATS

We performed adult hepatocyte transplantation (HCTx) and fetal liver t ransplantation (FLTx) into the spleens of hyperbilirubinemic Gunn rats in congenic combination and we compared the long-term effects of thes e procedures for as long as 12 months. Proliferative activity of intra splenic hepatocytes was evaluated using antiproliferating cell nuclear antigen (PCNA) immunohistochemical staining. The serum total bilirubi n 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 therea fter 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 t o 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), respectiv ely. Bilirubin glucuronides, which were not detectable in the bile fro m untreated Gunn rats, appeared in considerable amounts 4 months after HCTx and FLTx (27.5 % and 36.0 % of total bile, respectively). PCNA l abeling 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 l iver. In conclusion, both adult and fetal rat hepatocytes transplanted into the spleen in congenic combination functioned for at least a yea r in terms of bilirubin glucuronidation. The spleen is considered to b e one of the optimal grafting sites for hepatocytes, with nearly lifel ong significant function and proliferative activity.