Improved function of microencapsulated hepatocytes in a hybrid bioartificial liver support system

Abstract

Conventional methods of microencapsulating isolated hepatocytes with Type I collagen matrix have provided metabolic liver support in experimental animal models of acute liver failure and congenital metabolic liver disease. We compared the biological function of transplanted microencapsulated hepatocytes cultured on standard Type I collagen (Vitrogen) and a commercially available liver basement-membrane-like extract from a mouse sarcoma (Matrigel). Isolated hepatocytes were microencapsulated with Matrigel and Vitrogen within an alginate-poly-L-lysine composite membrane. Isolated encapsulated hepatocytes (IEH) were transplanted intraperitoneally into homozygous Gunn rats that exhibit congenital hyperbilirubinemia. Control Gunn rats received empty or no microcapsules. Total serum bilirubin and conjugated bilirubin in bile were measured at weekly intervals for one month. Significant (p < 0.01) decreases in total serum bilirubin were observed in all IEH transplanted animals. No such decrease was seen in control animals. Gunn rats that received Matrigel had significantly (p < 0.05) lower serum bilirubin values and significantly (p < 0.05) higher conjugated bilirubin in bile than those that received Vitrogen. We conclude that hepatocytes microencapsulated with Matrigel functioned better than those with Vitrogen. This improved in vivo biological response underscores the importance of using the appropriate cell attachment substratum to enhance the function of a hybrid bioartificial liver support system based on transplanted hepatocytes.