Fibroblasts play a crucial role in cutaneous wound repair (Martin,1997). These cells are attracted to wound sites by the localizedrelease of growth factors/cytokines such as platelet-derivedgrowth factor (Pierce et al., 1991). The first wave of fibroblastsenters the wound site along with sprouting vasculature. Thesecells differentiate into a specialized, but ephemeral, celltype called the myofibroblast (Sappino et al., 1990; Grinnell,1994).
Myofibroblasts, in response to monocyte/macrophage-derived factors,produce a provisional wound matrix that is enriched in fetal-likefibronectin and hyaluronan (Clark, 1990; Gailit and Clark, 1994;Juhlin, 1997; Singer and Clark, 1999). These cells also providethe motive force to contract the wound (Sappino et al., 1990).Myofibroblasts disappear from the wound site, apparently byapoptosis, and are replaced by a second wave of fibroblaststhat initiate the formation of a collagenous matrix (Grinnellet al., 1999). However, their ability to organize it is impaired,which results in the formation of scar tissue (Gailit and Clark,1994; Shah et al., 1994; Shah et al., 1995; Singer and Clark,1999). Fetal skin is repaired without scar formation (Adzickand Lorenz, 1994; Armstrong and Ferguson, 1995; Liechty et al.,2000). This is mainly owing to differences in fetal and adultfibroblast phenotypes (Schor et al., 1985; Olsen and Uitto,1989; Cullen et al., 1997; Gosiewska et al., 2001). The lowlevel of growth factors/cytokine production by fetal cells,especially TGF-ß1, appears to be a major factor inthe absence of scar formation (Shah et al., 1994; Shah et al.,1995; Eckes et al., 2000). The aberrant fibroblast phenotypealso appears to contribute to fibrotic disorders, such as keloidformation and scleroderma (Garner et al., 1993; Ghahary et al.,1994; Ghahary et al., 1996; Sollberg et al., 1994; Kirk et al.,1995; Nakaoka et al., 1995; Herrick et al., 1996; Hasan et al.,1997; Agren et al., 1999). Signals such as TGF-ß andconnective tissue growth factor play a significant role in thelatter process (Grotendorst, 1997).