Activities of human acidic fibroblast growth factor in an in vitro dermal equivalent model

Acidic fibroblast growth factor is a potent mitogen for human dermal fibroblasts in an in vitro three-dimensional collagen matrix, the "dermal equivalent." Both cell numbers and DNA synthesis are optimally stimulated by daily doses of 1 ng/ml of the pure human mitogen in the presence of heparin, which binds to, and stabilizes, the protein. Under daily treatment by 1 ng/ml aFGF, the fibroblast mitogenic response is marked but transient, and decreases steadily when fibroblasts mature in the collagen matrix. aFGF mitogenic stimulation also results in a decrease in cellular volume and inhibition of fibroblast-mediated contraction of the collagen gel. Various dosing regimes indicate that, although the greatest mitotic response was generated by daily dosing, nearly optimal responses can also be achieved with either a short duration of early daily dosing or longer-term intermittent treatment.