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: One hundred 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 CD90diffuse/CD34negative/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 CD90diffuse/CD34negative/minority phenotype, which is prolonged in pathologic scars. CD90+ fibroblasts are likely important players in cutaneous scarring. Correspondence: Jonathan Dale Ho, MBBS, DrSc, DipDermpath, 11 Geranium Path, Mona Heights, Kingston, Jamaica (e-mail: jdho@bu.edu). J. L. Browning and J. Bhawan contributed equally to this work. The authors declare no conflicts of interest. This paper is an original research and was conducted as part of a doctoral thesis. It is not under consideration for publication in any other journal. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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