Hepatic tissue engineering

Despite more than three decades of research and development, an artificial liver has not yet become clinical reality. Although previous attempts using a multiplicity of techniques including hemodialysis, hemoperfusion, plasma exchange, crosshemodialysis, and extracorporeal perfusion have shown minor improvement in patients with acute hepatic failure, clinical trials have failed to demonstrate any survival benefit. More recent efforts have been directed at the use of hepatocytes as the basis of liver support. A primary problem with these cell-based approaches that involves the use of hepatocyte in liver assist devices is the eventual loss of differentiated phenotype. Our strategy is to target this fundamental problem by developing a bioartificial liver that incorporates highly-differentiated hepatocytes. The effect of fluid flow on cultured hepatocytes as well as the development of micro-channels due to the high metabolic need of hepatocytes for oxygen will also be discussed. Finally, the efficacy of hepatic tissue engineered micro-reactors in small animal studies of liver failure will be presented. In summary, this presentation will take a critical look at past and present concepts in the development of hepatocyte-based artificial liver assist systems, and review the ongoing work on hepatic tissue engineering in our laboratory.