Long-term differentiated function of heterotopically transplanted hepatocytes on three-dimensional polymer matrices

Hepatocyte transplantation using porous matrices is under investigation as an alternative therapy for certain liver diseases. For this purpose, long-t erm function of transplanted hepatocytes is mandatory. This problem has not been sufficiently investigated yet. In this study Lewis rats were used as donors and recipients. Stimulated (group A, portocaval shunt) or unstimulat ed (group B) hepatocytes were transplanted into prevascularized polyvinyl-a lcohol matrices. Cell-free matrices served as controls (group C). Matrices were harvested between 1 h and 1 year after implantation and analyzed by mo rphometry; albumin RNA in situ hybridization; and cytokeratin-, actin-, des min-, and macrophage-specific antigen immunohistology. The hepatocyte numbe r significantly decreased within the first week following implantation. Bet ween 1 month and 1 year after transplantation a significant increase in hep atocyte number was noted in groups A and B. Albumin transcripts of transpla nted hepatocytes were at normal levels at all times except for group B afte r 1 year. The immunohistology suggested engraftment of nonparenchymal liver cells. We conclude that 3-dimensional matrices provide a sufficient enviro nment for long-term engraftment of transplanted liver cells. The hepatocyte s are able, despite suboptimal initial engraftment, to repopulate the scaff old for at least half of the recipient's life span and maintain cell-specif ic function after sufficient stimulation. (C) 1999 John Wiley & Sons, Inc.