Stimulating effects of fibroblast growth factors on hepatic function of fetal liver cells synergistically with oncostatin M in three-dimensional culture

Fetal liver cells (FLCs) are regarded as a feasible cell source of bioartificial liver (BAL), because the FLCs have proliferating ability even in vitro. However, the cellular functions of FLCs are considerably lower compared with mature hepatocytes. Thus, maturation of cultured FLCs is essential for enhancing the performance of the BAL using the FLCs. In the present study, the effects of fibroblast growth factors (FGF-1, FGF-2, and FGF-4) on cell growth and the liver-specific functions of mouse FLCs were investigated in the presence or absence of oncostatin M (OSM), under both three-dimensional (3-D) and monolayer culture conditions. When FGF-2 was used, no stimulating effects on the albumin secretion activities of the FLCs were observed either in the 3-D or monolayer cultures, although cell growth was improved in these cultures. In the cases of FGF-1 and FGF-4, these factors also had no effect on the albumin secretion activities in the absence of OSM. However, in the presence of OSM, FGF-1 and FGF-4 significantly enhanced the activities of the FLCs but only in the 3-D cultures. From scanning electron microscopic observation, the 3-D culture FLCs formed big cell aggregates on the surface of a porous scaffold. In conclusion, it was clarified that FGF-1 and FGF-4 facilitate the maturation of 3-D culture FLCs synergistically with OSM.