HEPATOCYTE TRANSPLANTATION USING POLY-GLY COLIC ACID POLYMER MATRICESIN THE RAT UNABLE TO SYNTHESIZE L-ASCORBIC-ACID

Hepatocyte Transplantation (HTX) with biodegradable poly-glycolic acid (PGA) polymer matrices was performed using a scurvy-prone ODS (Osteog enic Disorder Shionogi) rat model. Portacaval shunt was created prior to HTX to stimulate the engraftment and proliferation of the hepatocyt es implanted between the mesenteric leaves of the small intestine. The histology showed numerous layers of successfully engrafted hepatocyte s at 8 weeks after HTX. The plasma L-ascorbic acid (AsA) concentration in the HTX group was 0.90+/-0.11 mu g/ml at 4 weeks after cessation o f AsA supplementation, which was statistically significantly higher co mpared to the control (0.43+/-0.10 mu g/ml, p<0.01). The body weight r atio at the same time point was also significantly higher in the HTX g roup (1.12+/-0.03 vs. 0.92+/-0.02, p<0.05). Auxiliary heterotopic part ial liver transplantation (HLT) was performed to compare the results w ith the HTX experiment. Right lobes were used as a graft which consist ed approximately 20% of the whole liver mass. The control rats transpl anted with enzyme-deficient grafts showed rapid weight loss and physic al signs of scurvy as early as 2 weeks after the operation. On the oth er hand, the rats with normal liver grafts grew normally and their pla sma AsA level at week 4 (2.96+/-0.36 mu g/ml) was not different from t he value obtained from the whole liver transplanted group (2.67+/-0.42 mu g/ml). The ODS rat model is useful to evaluate the effectiveness o f HTX.