Wound fluid amino acid concentrations regulate the effect of epidermal growth factor on fibroblast replication

Growth factors and amino acids (AA) are required for cell proliferation. A comparison of the AA composition of wound fluid (WF) to that of Eagle's medium reveals that AA in WF may be limiting to cell replication. Yet WF supports fibroblast replication and stimulates AA uptake. Epidermal growth factor (EGF) stimulates fibroblast replication and stimulates human wound healing when applied topically. We evaluated the interactions between EGF and AA concentrations found in WF. Wound fibroblasts were cultured in media prepared to mimic the AA concentrations found in WF on days 1, 5, and 10 and in the presence of varying concentrations of EGF. Fibroblasts cultured in all three experimental media showed a dose response to EGF for both tritiated-thymidine uptake (proliferation) and AA uptake. The fibroblast proliferation in response to EGF was augmented by the AA composition of day-5 WF. These data show a dose-dependent effect of EGF on fibroblast replication and AA uptake in the absence of serum that is augmented by the particular AA combination found in day-5 WF and suggests that an optimal physiologic AA profile may aid in EGF stimulation of wound fibroblast replication.