Trophic effect of multiple growth factors in amniotic fluid or human milk on cultured human fetal small intestinal cells

Objectives: To evaluate the role of growth factors in amniotic fluid and in human milk on gastrointestinal adaptation of the fetus and very low-birth-weight infants, the effects of these fluids and multiple growth factors were investigated in a human fetal small intestinal cell line (FHs 74 Int). Methods: After FHs 74 Int cells were incubated with amniotic fluid, human milk, or recombinant growth factors, growth-promoting activity was measured by [H-3]-thymidine incorporation into cells. Results: Incubating cells with amniotic fluid or human milk promoted growth dose dependently. Genistein almost completely inhibited growth-promoting activity in amniotic fluid (P = 0.002), and growth was partially inhibited by antibodies against epidermal growth factor (EGF) (P = 0.047), insulinl-ike growth factor-1 (IGF-1, P = 0.047), or fibroblast growth factor (FGF, P = 0.014). This activity in human milk was inhibited almost completely by genistein (P < 0.0001) and partially inhibited by antibodies against EGF (P = 0.036), IGF-1 (P = 0.009) FGF (P = 0.004), hepatocyte growth factor (HGF, P = 0.001), or transforming growth factor-alpha (TGF-alpha, P = 0.001). Although recombinant EGF, IGF-1, FGF, HGF, and TGF-a elicited a synergistic trophic response on cultured cells, the response was much less than with amniotic fluid or with human milk. Conclusion: In aminiotic fluid and in human milk, EGF, IGF-1, FGF, HGF, and TGF-alpha have a strong trophic effect on immature intestinal cells and may be involved in perinatal gastrointestinal adaptation.