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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 [3H]-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), insulin-like 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 h 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-&agr; (TGF-&agr;, P = 0.001). Although recombinant EGF, IGF-1, FGF, HGF, and TGF-&agr; 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-&agr; have a strong trophic effect on immature intestinal cells and may be involved in perinatal gastrointestinal adaptation.