Improvement of the effect of hepatocyte isograft in the Gunn rat by cotransplantation of islets of Langerhans.

PURPOSE

Hepatocyte transplantation (HcTX) has been investigated for many years as an alternative therapy to orthotopic liver transplantation to treat hepatic congenital enzymatic deficiency disease. The animal model most used is the Gunn rat, which presents a hyperbilirubinemia caused by the lack of uridine-diphosphate-glucuronyl-transferase. Some investigators have clearly described a hepatotrophic effect mediated by islets of Langerhans (IL) when transplanted with hepatocytes (Hc). In this study, the functional effect of cotransplanted IL on hepatocytes (co-HcTX) in Gunn rats in an isograft model is assessed.

METHODS

Two groups are compared: group 1 (n = 6), HcTX to group 2 (n = 6), co-HcTX. Cells isolated by enzymatic digestion are transplanted directly into the splenic parenchyma. Blood samples are taken regularly until day 100 to measure the unconjugated bilirubin (UB). Histological examination of the spleen is performed at the end of the experiment.

RESULTS

Both groups show a significant decrease of the UB: group 1, 47%; group 2, 65%. The decrease is statistically more pronounced with co-HcTX. The histological analysis shows a trophic effect of the IL on the grafted hepatocytes in the co-HcTX group.

CONCLUSIONS

The HcTX and the co-HcTX correct partially the hyperbilirubinemia of the Gunn rat. A functional assessment has been performed to evaluate the effect of cotransplanted IL on HcTX.