[Hepatocellular transplantation in rats with congenital ascorbic acid deficiency]

The purpose of this study was to investigate suitable sites for hepatocyte transplantation in rats with congenital liver enzyme deficiency. Hepatocytes were isolated from ODS-(+)/+ rats, which are congenic to ODS-od/od rats and have hepatic L-gulonolactone oxidase. A total of 1 x 10(7), 1 x 10(7), and 2.5 x 10(6) hepatocytes were respectively transplanted into the peritoneal cavity, spleen, or portal vein of ODS-od/od rats, which are unable to synthesize ascorbic acid (AsA) due to lack of hepatic L-gulonolactone oxidase. After 4 days of oral pretreatment with 0.05% 2-acetylaminofluorene, recipients underwent 70% partial hepatectomy just before transplantation. AsA administration was discontinued at 6 weeks after transplantation. The symptom-free survival rate and the serum AsA level of recipient rats were determined at 6 weeks after discontinuing AsA administration. The symptom-free survival rate of untransplanted rats and recipient rats with intraperitoneal, intrasplenic and intraportal hepatocyte transplantation were 0%, 0%, 60%, and 100%, respectively. The serum AsA levels were 0.20 +/- 0.20 microgram/ml, 0.14 +/- 0.05 microgram/ml, 1.06 +/- 0.26 microgram/ml, and 1.58 +/- 0.61 microgram/ml, respectively. Intrasplenic or intraportal transplantation was able to cure ODS-od/od rats. A subsequent splenectomy study showed that hepatocytes reaching the liver via the splenic vein following intrasplenic hepatocyte transplantation played a major role in this experimental success.