FIBROBLAST-MIGRATION IN A WOUND MODEL OF ASCORBIC ACID-SUPPLEMENTED 3-DIMENSIONAL CULTURE SYSTEM - THE EFFECTS OF CYTOKINES AND MALOTILATE,A NEW WOUND-HEALING STIMULANT, ON CELL-MIGRATION

To assess the migratory response of fibroblasts in vitro, normal human dermal fibroblasts (NHDF) were cultured in the presence of L-ascorbic acid 2-phosphate to induce a multilayered structure. Round wounds wer e made by punching, and the migratory response was evaluated by counti ng the number of migrating cells in the wounded areas. Collagenase act ivity in the culture-medium was then measured. When the wound model wa s treated with bFGF, IL-1 alpha or PDGF, the migratory response was fa cilitated with increased collagenase secretion. In contrast, treatment with TGF-beta reduced the migratory response and collagenase secretio n. Since the multilayered structure is rich in collagenous matrix, deg radation of the matrix by secreted collagenase is probably necessary f or the cells to migrate into the wounded areas. Furthermore, malotilat e, which is now under development as an agent for wound therapy, facil itated the migratory response of NHDF with increased collagenase secre tion in this wound model, suggesting that the wound healing effect of malotilate is in part attributable to stimulated migration of fibrobla sts to wounded areas subsequent to extracellular matrix-degradation. ( C) 1998 Elsevier Science Ireland Ltd. All rights reserved.