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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 hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and 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 hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, 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 TGFβ1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars.

SUBMITTER: Plotczyk M

PROVIDER: S-EPMC9822907 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue.

Plotczyk Magdalena M Jiménez Francisco F Limbu Summik S Boyle Colin J CJ Ovia Jesse J Almquist Benjamin D BD Higgins Claire A CA

NPJ Regenerative medicine 20230106 1

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 hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissu ...[more]

PMID: 36609660

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Project description:Secondary hair follicles (SHFs) in cashmere goats produce high-value cashmere fibers, which cyclic regulation is critical for optimizing cashmere yield and quality. This study explores the phenotypic changes and differential protein expression profiles involved in the telogen-to-anagen transition of SHFs. Through histological observations, proteomic analyses, and immunohistochemical validation, we identified key molecular features and regulatory pathways underlying SHF cyclic renewal. Histological analysis showed that telogen-phase SHFs exhibit a reduced volume, decreased dermal papilla cell (DPC) and hair matrix cell (HMC) activity, compact structure, and superficial localization in the dermis. Anagen-phase SHFs exhibit significantly increased volume, deeper dermal penetration, and active cell proliferation. Proteomic analysis identified 3,654 proteins in skin samples, with 458 differentially expressed proteins (DEPs) significantly associated with biological processes such as cell adhesion, signal transduction, protein synthesis, and metabolism. These DEPs were enriched in key regulatory pathways, including Notch, Wnt, Jak-STAT, PI3K-Akt, and ECM-receptor interaction. Protein-protein interaction analysis identified A Disintegrin and Metalloproteinase Domain 17 (ADAM17), Secreted Frizzled-Related Protein 1 (SFRP1), and Protein Phosphatase 1 Catalytic Subunit Alpha (PPP1CA) as core regulators of SHF cyclic transitions. Validation by RT-qPCR, Western blot, and immunohistochemical analyses confirmed that ADAM17, SFRP1, and PPP1CA were predominantly localized in functional regions, including the outer root sheath (ORS), dermal papilla (DP), and hair matrix (HM). Their expression levels were significantly enhanced during anagen. ADAM17 is suggested to promote the growth of SHFs by regulating ORS cells proliferation and mediating signal transduction in DPCs, while SFRP1, as a modulator of the Wnt signaling pathway, likely supports SHFs growth and regeneration by modulating the activity of Secondary hair follicle stem cells (SHFSCs) and promoting the differentiation of HMCs. PPP1CA may enhance cell proliferation and metabolic activity by modulating phosphorylation states. In conclusion, this study identifies key molecular factors and pathways driving the telogen-to-anagen transition in cashmere goat SHFs. It emphasizes the roles of ADAM17, SFRP1, and PPP1CA in SHF renewal and offers insights into SHF development mechanisms and cashmere fiber improvement.

Dataset Information

Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue.

Publications

Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue.

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