Extensive CD34-to-CD90 Fibroblast Transition Defines Regions of Cutaneous Reparative, Hypertrophic, and Keloidal Scarring.

Background: CD90(+) fibroblasts have been described arising from and replacing the homeostatic CD34(+) network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. Objectives: To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. Methods: Ohundred and seventeen scars (reparative/hypertrophic/ keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90(+)/CD34(+) transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/ procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. Results: Most scars demonstrate a CD90(diffuse)/CD34(negative/minority) pattern, and dual CD90(+)/CD34(+) fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34(+)/CD90(-) state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90(+) and SMA(+) fibroblasts collagenize scars, although CD90(+) fibroblasts are more prevalent. Conclusions: CD90(+) fibroblasts likely arise from the resting CD34(+) fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90(diffuse)/CD34(neg)(ative/minority) phenotype, which is prolonged in pathologic scars. CD90(+) fibroblasts are likely important players in cutaneous scarring.