Hepatic Tissue Engineering

We are interested in understanding the structure/function relationship of the liver to improve cell-based therapy for liver disease and develop in vitro models of liver tissue. Because of the complexity of the liver architecture and the inadequate therapies for liver disease, we have focused on a cell-based approach. Progress in development of such therapies has been stymied by the tendency of primary liver cells (hepatocytes) to rapidly lose their viability and phenotype upon isolation from the complex in vivo microenvironment of the liver. W e are therefore interested in how the microenvironment around hepatocytes affects cell fate and function. We utilize microfabrication tools (methods developed to manufacture microelectronic circuits) to control and study the role of cell-cell interactions , cell-extracellular matrix interactions, and soluble stimuli (e.g. O2) on hepatocyte function. We are also developing systems to extend our findings in two-dimensional tissues to three-dimensional constructs using photopolymerized hydrogels . Finally, due to the limited growth of hepatocytes in vitro, we are interested in stem cell sources of hepatocytes. Collectively, these studies will provide a rational approach to hepatic tissue engineering.