Trophic Effect of Multiple Growth Factors in Amniotic Fluid or Human Milk on Cultured Human Fetal Small Intestinal Cells

Department of Pediatrics, Osaka City University, Ōsaka, Ōsaka, Japan
Journal of Pediatric Gastroenterology and Nutrition (Impact Factor: 2.63). 05/2002; 34(5):524-8. DOI: 10.1097/00005176-200205000-00010
Source: PubMed


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).
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.
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 < 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-alpha elicited a synergistic trophic response on cultured cells, the response was much less than with amniotic fluid or with human milk.
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.

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    • "Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, it remains an important objective to define the nature and amount of enteral diet that is required postnatally to facilitate optimal intestinal tolerance. Similar to breast milk, amniotic fluid may contain important immunomodulatory, growth and antimicrobial factors (Akinbi et al., 2004; Hirai et al., 2002) that may act similarly to facilitate tolerance to bacterial antigens and dampen excessive TLR-mediated responses in the perinatal period. Continuation of fetal amniotic fluid intake after birth, as a mode of minimal enteral nutrition during TPN, has been suggested (Barney et al., 2007), but never tested in controlled studies, partly due to obvious practical difficulties in procuring un-interrupted supplies. "
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    Veterinary Immunology and Immunopathology 06/2014; 159(3-4). DOI:10.1016/j.vetimm.2014.02.012 · 1.54 Impact Factor
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    • "Compared to other growth factors, HAF is less expensive and more readily available. This fluid is a natural and enriched human source of various growth factors with synergistic effects (Underwood et al., 2005; Hirai et al., 2002; Park et al., 2006). HAF has an approximately neutral pH (7.2), and its osmotic pressure is in the physiological range. "
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    • "From the 14 th to 16 th weeks of gestation, HAF consists of multiple trophic factors essential for fetal growth and embryonic cell proliferation and differentiation [22] [27]. For example, Hirai et al. (2002) found that multiple growth factors in HAF promote the growth of human fetal small intestinal cells in culture [28]. It also seems that some HAF components, such as fibronectin (the 3 rd most abundant protein in HAF in the 16 th week of gestation [23]), plays a pivotal role in cell attachment, polarity, and migration [29]. "
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