A review of the influence of growth factors and cytokines in in vitro human keratinocyte migration

Objective: Keratinocyte migration from the wound edge is a crucial step in the reepithelization of cutaneous wounds. Growth factors and cytokines, released from cells that invade the wound matrix, play an important role, and several in vitro assays have been performed to elucidate this. The purposes of this study were to review in vitro human studies on keratinocyte migration to identify those growth factors or cytokines that stimulate keratinocyte migration and whether these assays might serve as a screening procedure prior to testing combinations of growth factors or cytokines to promote wound closure in vivo. Methods: Research papers investigating effect of growth factors and cytokines on human keratinocyte migration in vitro were retrieved from library sources, PubMed databases, reference lists of papers, and searches of relevant journals. Results: Fourteen different growth factors and cytokines enhanced migration in scratch wound assay and HGF together with TGF-beta, and IGF-1 with EGF, were more stimulatory than either growth factor alone. HGF with TGF-beta 1 had a greater chemokinetic effect than either growth factor alone in transmigration assay. TGF-beta 1, FGF-7, FGF-2 and AGF were chemotactic to keratinocytes. EGF, TGF-alpha, IL-1 alpha, IGF and MGSA enhanced cell migration on ECM proteins. Conclusion: Many growth factors and cytokines enhanced migration of keratinocytes in vitro, and certain combinations of growth factors were more stimulatory than either alone. These and other combinations that stimulate keratinocyte migration in vitro should be tested for effect on wound closure and repair in vivo. The scratch wound assay provides a useful, inexpensive and easy-to-perform screening method for testing individual or combinations of growth factors. or cytokines, or growth factors combined with other modalities such as laser irradiation, prior to performing wound healing studies with laboratory animals. (C) 2013 Elsevier Ltd. All rights reserved.