It is worth investigating heterotypic cell cell interactions by mimicking their in vivo environment. In the present study, the mechanism of functional enhancement was investigated in a hepatocyte fibroblast coculture with respect to the contributions of soluble factors. The enhanced hepatic functions through heterotypic interactions are effective by increasing fibroblast proliferation separately cocultured in 3D silica fabrics. The important roles of active soluble factors in heterotypic cell communications were suggested by this study using 3D proliferated tissues with satisfactory physiological morphologies in silica fabrics.