CD26+FAP+ fibroblasts increase ECM expression in keloid scarring

Keloids are fibrotic scars characterised by excessive fibroblast proliferation, extracellular matrix (ECM) deposition and growth beyond the original wound site. Fibroblasts are thought to be the main cell type responsible for keloid formation. However, dermal fibroblasts are a heterogeneous population of cells and to date, the distinct fibroblast subsets involved in keloid formation remain to be determined. Thus, our aim was to characterise the different stromal cell populations in healthy human dermis and keloid scars. We were particularly interested in CD26 as a marker of fibroblasts with intrinsic fibrogenic potential, given fibroblasts expressing CD26 are responsible for ECM deposition during wound healing in mice. We initially used 15-colour flow cytometry to investigate the stromal cell populations derived directly ex vivo from healthy human dermis and keloid scars. We identified a distinctive CD26+ FAP+ CD90+ fibroblast population in keloid scars and in healthy human dermis. Multicolour immunofluorescence microscopy revealed that these CD26+ FAP+ CD90+ cells form the bulk of the keloid mass. After sorting these uncultured cells directly from healthy skin and keloid scars we analysed their transcriptomes by RNA sequencing. CD26+ FAP+ CD90+ cells in keloid scars had much higher expression of ECM genes than those cells from healthy dermis. We conclude that a distinctive CD26+ FAP+ CD90+ population of fibroblasts found in both healthy human dermis and keloid scars is likely to be the major source of ECM deposition in keloid scarring. Purification and molecular characterisation of these fibrogenic cells directly from keloid scars is likely to suggest novel strategies to treat keloid scarring.