Anagen Hair Follicles Transplanted into Mature Human Scars Remodel Fibrotic Tissue

Abstract

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hair‑bearing skin undergoes physiological remodeling during the regular cycling of hair follicles. In a pilot clinical study, we tested if anagen hair follicles transplanted into human scars can actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full‑thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that anagen hair follicles induced an increase in the epidermal thickness, interdigitation of the epidermal‑dermal junction, dermal cell density, and vessel density. Remodeling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibers, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro‑fibrotic factors TGF‑β1, IL‑13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing therapeutic approaches to remodel mature scars.