Optimization Of Hepatic Function In Co-Cultures

Abstract

Clinical implementation of hepatocyte-based bioreactors has historically been limited by (1) stability of hepatic function necessitating expensive ‘cartridge’ replacements every few hours (Rozga et al, 1994), (2) limited ability to scale-up (Nyberg et al, 1993; Wu et al, 1995), (3) large reactor volume causing dilution of hepatocyte products (Takahashi et al, 1992) and (4) adequate cell source (for recent reviews see- Rozga et al, 1993; Sussman and Kelly, 1995; Jauregui et al, 1996). A novel co-culture based bioreactor should address each of these limitations. We have shown previously that co-cultivation of hepatocytes with 3T3-J2 fibroblasts yielded stable hepatic function on the order of weeks to months. Furthermore, microfabrication techniques such as those utilized here offer unique advantages for scale-up by replication of many, identical units as seen in the integrated circuit industry. Here, we address the optimization of co-cultures to minimize reactor volume and to maximize cell function (minimize necessary cell source).