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Rat hepatocytes in a collagen-gel sandwich configuration were exposed to silicon alkoxides in a gas phase, yielding a 0.05 to 0.15 microm porous silica layer on the gel surface. Cell viability was unaffected by the procedure. After 24 h, bilirubin conjugation, ammonia removal, urea synthesis, and diazepam metabolism were unaffected by the procedure. However, both the ammonia removal rate and diazepam metabolism were increased after 48 hr, whereas urea synthesis was unaffected. These data indicate that silica overlay allows efficient metabolic activity of collagen-gel entrapped hepatocytes. The fact that the KM of bilirubin conjugation was unaffected by the presence of the silica membrane suggests that the transport of albumin-bound substrates is not decreased. The enhancement in some metabolic activities found 48 h after the entrapment procedure may be the result of favorable changes in the hepatocyte microenvironment. These characteristics might be useful for the development of organotypical bioartificial liver devices.

Background: Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs., Methods: Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min., Results: The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal., Conclusion: . These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.