Effect of human basic fibroblast growth factor on fibroblast proliferation, cell volume, collagen lattice...

Human recombinant basic fibroblast growth factor (bFGF) is a potent mitogen for normal human dermal fibroblasts in the presence of heparin which binds to and stabilizes it. The optimal mitotic response is obtained with a concentration of 1 ng/ml of bFGF in monolayer cultures (non-differentiated fibroblasts) as well as in the better-differentiated fibroblasts obtained through the 'collagen lattices' culture system (fibroblasts embedded in a 3-dimensional collagen gel) achieving a doubling of the cell number in 8 days. Despite increasing the number of cells, bFGF decreases the ability of fibroblasts to contract collagen fibers. This inhibition is concentration-dependent and reaches a plateau at a dose of about 1 ng/ml. This effect is associated with a bFGF-induced decrease of fibroblast volume. Various dosing regimens indicate that although the highest response was obtained by daily dosing nearly optimal response was obtained either by early daily dosing or short intermittent treatment. Interestingly, the fibroblast mitotic response to bFGF decreases steadily when fibroblasts mature in collagen gels. The mitogenic properties of bFGF associated to its ability to inhibit fibroblasts contraction, if demonstrated in vivo, may be of interest in the management of wound healing.