Improved survival and ammonia metabolism by intraperitoneal transplantation of microencapsulated hepatocytes in totally hepatectomized rats

Background. We evaluated the effects of intraperitoneal transplantation of microencapsulated hepatocytes in a 3-stage total hepatectomy rat model. Methods. A new model of total hepatectomy was created as follows. First, th e infrahepatic inferior vena cava was ligated just above the fight renal ve in. Seven days later, the portal vein was ligated and a portacaval shunt wa s established using a Teflon catheter over a venipuncture needle. Another 7 days later, total hepatectomy was completed by ligating and dividing the s uprahepatic inferior vena cava, the hepatic artery, and the bile duct. Next , 4 x 10(7) hepatocytes (4 % of the normal liver hepatocyte mass) isolated from male Wistar rats were microencapsulated within a collagen matrix envel oped by a 3-layer membrane of sodium alginate-poly-L-lysine-sodium alginate copolymer Capsules containing hepatocytes (diameter, 500-800 mum) and empt y capsules (control) were transplanted intraperitoneally 4 days before the total hepatectomy. Survival time and selected blood chemistry concentration s after the total hepatectomy were measured. The capsules were also examine d histologically with hematoxylin and eosin staining and modified Gmelin's stain for bile pigments. Results. The survival time was greater in the rats given the microencapsula ted hepatocytes than in the control rats (17.3 +/- 3 vs 3.7 +/- 0.1 hours; P < .01). The blood ammonia concentrations increased soon after total hepat ectomy but remained significantly lower in the rats with microencapsulated hepatocytes (P < .05). The microcapsules contained numerous viable hepatocy tes with abundant bile pigments and no lymphocytic infiltration. Conclusions. Microencapsulated hepatocytes with an ultrathin polymer layer that protects them from inflammatory and lymphocytic reactions may facilita te their ability to function. In this study, 4 x 10(7) hepatocytes signific antly prolonged the survival of rats that underwent hepatectomy and support ed ammonia metabolism. Further development of this technique may permit its use in patients with hepatic failure.