Hepatocyte autotransplantation into spleen using cirrhotic rats

Syngeneic rat hepatocytes transplanted into different sites such as spleen, peritoneum, lung and pancreas have proved to proliferate and provide some liver functions to correct congenital liver disorders or acute liver failure. In a previous series in which hepatocytes from Lewis rats were allotransplanted into cirrhotic Wistar-Furth rats, we showed that the most effective immunosuppressive dosage is 12 mg/kg cyclosporine A three times a week. However, it is yet to be demonstrated whether hepatocytes can be kept longer than 180 days, and 50% hepatectomy is always required. In this study, the feasibility of autotransplantation of hepatocytes in cirrhotic Wistar rats is evaluated. After viability was determined by trypan blue exclusion, 5 x 10⁶ hepatocytes were injected. Rats were sacrificed and their spleens removed between 7 and 180 days after autotransplantation, at which time they were assessed on the basis of periodic acid-schiff reaction and levels of cytokeratin A₁-A₃, cytokeratin 19 and technetium 99 uptake. A good Tc-99 uptake was observed, but there was no evidence of either complete bile ductular-like structures or significantly improved laboratory findings. Our study has shown that autotransplantation is feasible and is associated with long-term hepatocyte survival. However, as confirmed by the experiences of Mite and coworkers in humans, the fate of hepatocytes after six months remains uncertain, and the harvesting of hepatocytes from severely cirrhotic livers entails a series of problems.