Outstaying their Welcome: The Persistent Myofibroblast in IPF.

As noted, the unrestrained accumulation of myofibroblasts is a key feature that differentiates fibrotic from physiologic repair. The accrual of these cells represents the combined effects of cell trafficking, proliferation and death. Of these, proliferation has received considerable attention; indeed, fibroblastic foci were initially defined as “small aggregates of actively proliferating fibroblasts and myofibroblasts” [11,12]. Certainly, studies suggest that fibroblast proliferation is important, especially in the early phases of wound repair and fibrosis [13]. Moreover, soluble mediators implicated in fibrosis have been shown to induce fibroblast proliferation in vitro [14-16]. Comparisons of IPF and normal lung fibroblasts, however, have shown variable results, and some studies suggest that IPF fibroblasts actually have a decreased rate of proliferation [17,18]. Moreover, studies of IPF tissue have demonstrated that while there is substantial epithelial cell proliferation, there is little to suggest robust fibroblast proliferation within fibroblastic foci [19,20].