Distinguishing fibroblast promigratory and procontractile growth factor environments in 3-D collagen matrices

Understanding growth factor function during wound repair is necessary for the development of therapeutic interventions to improve healing outcomes. In the current study, we compare the effects of serum and purified growth factors on human fibroblast function in three different collagen matrix models: cell migration in nested matrices, floating matrix contraction, and stressed-released matrix contraction. The results of these studies indicate that platelet-derived growth factor (PDGF) is unique in its capacity to promote cell migration. Serum, lysophosphatidic acid, sphingosine-1-phophate (S1P), and endothelin-1 promote stressed-released matrix contraction but not cell migration. In addition, we found that S1P inhibits fibroblast migration and treatment of serum to remove lipid growth factors or treatment of cells to interfere with S1P(2) receptor function increases serum promigratory activity. Our findings suggest that different sets of growth factors generate promigratory and procontractile tissue environments for fibroblasts and that the balance between PDGF and S1P is a key determinant of fibroblast promigratory activity.