In vitro characterization of porcine hepatocyte function

The clinical consequences of acute liver failure are associated with high m ortality. Intensive medical intervention is required to treat the symptoms of liver failure, including coagulopathy, metabolic instability, and enceph alopathy. Providing temporary liver support with an extracorporeal liver as sist device could stabilize the patient until a donor liver became availabl e or the patient's own liver was able to recover. The use of human hepatocy tes as the biologic component of the assist device is precluded by the scar city of available tissue and the limited proliferative potential of adult h epatocytes in vitro. Consequently, porcine hepatocytes are being evaluated as a cell source for liver assist devices. Maintaining differentiated funct ion in isolated hepatocytes, however, remains a challenge in the developmen t of this technology and is complicated by the fact that the key therapeuti c functions for short-term survival have not been well defined. Several app roaches have been effective in prolonging rodent hepatocyte function in vit ro, including manipulation of extracellular matrix. Here, we have investiga ted porcine hepatocyte function in vitro with a specific emphasis on the re sponse to exogenous collagen matrix. In control cultures, albumin secretion increased during the first 7-10 days of culture to an average of 50 +/- 17 mu g/day/10 degrees cells and then decreased over the next 2 weeks. The pa ttern of urea synthesis was slightly different in that it was highest in th e first 1-3 days postisolation (140 +/- 19 mu g/day/10(6) cells) and then d ecreased by about 50% to a plateau level that was stable during the next 3- 4 weeks of culture. Cytochrome P450-mediated activities were the most labil e with time in culture and were undetectable after the first week in the ab sence of pharmacological inducers. In contrast to results reported for rat cells. porcine hepatocytes exhibited differentiated function in the absence of any modification of the culture dish surface and function was not incre ased or prolonged in the presence of exogenous collagen.