Motogenic substrata and chemokinetic growth factors for human skin cells

Abstract

Extracellular matrix remodelling and accurate spatio-temporal coordination of growth factor expression are two factors that are believed to regulate mitoses and cell migration in developing and regenerating tissues. The present quantitative videomicroscopical study examined the influence of some of the principal components of extracellular matrix and several growth factors that are known to be expressed in dermal wounds on three important facets of human skin cell behaviour in culture. Keratinocytes, melanocytes and dermal fibroblasts (and myofibroblast controls) exhibited varying degrees of substrate adhesion, division and migration depending on the composition of the culture substrate. Substrates that are recognized components of transitional matrices generally accentuated cell adhesion and proliferation, and were motogenic, when compared with serum-treated control surfaces, whereas components of more stable structures such as basement membrane had less influence. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and α fibroblastic growth factor ( α FGF) all promoted cell proliferation and were chemokinetic to dermal fibroblasts, but not keratinocyte growth factor (KGF) or transforming growth factor β (TGF β ). PDGF, EGF and KGF, but not TGF β or α FGF, all enhanced proliferation of dermal keratinocytes.The same growth factors, and in addition KGF, all stimulated motility in keratinocytes, but TGF β and α FGF again had no effect. Developing a better understanding of the interdependency of factors that control crucial cell behaviour may assist those who are interested in the regulation of histogenesis and also inform the development of rational therapeutic strategies for the management of chronic and poorly healed wounds.

Growth substrate induced functional changes elucidated by FTIR and Raman spectroscopy in in–vitro cultured human keratinocytes

“…They have found that surface chemistry can affect integrin binding of the cell to the substrate even when utilising the same coating molecule. Sutherland et al [53] have also analysed proliferative effects in human keratinocytes, melanocytes, fibroblasts and myofibroblasts adherent to fibronectin, laminin, collagen and vitronectin with similar results to our work. [6], where increases in protein and decreases in lipid were observed in proliferating cells, with decreases in RNA and increases in DNA between plateau and exponential phase cells.…”

Fibronectin Expression Determines Skin Cell Motile Behavior

“…Previously, it was demonstrated that FN expression decreased in fibroblastic cells with increasing passages and transformation ( Yamada et al , 1977 ). Increased passage number in human keratinocytes has also been demonstrated to correspond to increased migration rates ( Sutherland et al , 2005 ). We therefore assessed the FN expression and motility rates of human primary keratinocytes with increasing passage number (p2–p3, 11–16 days post isolation.…”

Wound re-epithelialization: modulating kerationcyte migration in wound healing

“…It should be mentioned that the growth factors and cytokines provide motogenic stimulation for keratinocytes that are adherent to matrix, and thus the nature of the matrix on which they are adhered modulates the motogenic response. Numerous studies have demonstrated that the composition of the underlying extracellular matrix can modify the speed of keratinocyte migration in the presence of growth factors (103,(125)(126)(127)(128)(129)(130)(131). Mechanisms by which this occurs include synergistic activation of kinase cascades that converge upon migration (132), and upregulation of specific integrins that contribute to a motile phenotype by the growth factors (95).…”