Human amniotic fluid stimulates the proliferation of human fetal and adult skin fibroblasts: the roles of bFGF and PDGF and of the ERK and Akt signaling pathways.

Fetuses and adults follow different repair strategies for the healing of skin wounds. Experimental evidence indicates that this most probably reflects the intrinsic characteristics of fetal tissue, although environmental factors may also contribute to this phenomenon. Accordingly, the aim of the present study was to investigate the effect of the in utero environment, i.e., amniotic fluid, on one of the major parameters of wound healing, namely cell proliferation, and especially its effect on cultures of both human fetal and adult skin fibroblasts. We found that second trimester human amniotic fluid is a potent stimulant of DNA synthesis and proliferation of cells from both developmental stages. This effect is due to the presence of growth factors, especially basic fibroblast growth factor and platelet-derived growth factor, because inhibitors of their respective receptor kinases and specific neutralizing antibodies can significantly inhibit cell proliferation. Furthermore, we found that this mitogenic effect is mediated through the activation of the MEK/ERK and the PI3K/Akt signaling pathways. Interestingly, we have not observed any significant differences between fetal and adult fibroblasts in their response to amniotic fluid, indicating that cells from both developmental stages respond equally to this complex mixture of regulatory molecules.