Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: 2005- : Amsterdam : Elsevier Science
      Original Publication: Amsterdam, North Holland Pub. Co.
    • Subject Terms:
      Fibroblasts*/drug effects ; Skin Transplantation*/methods ; Cellular Senescence*/drug effects ; Neovascularization, Physiologic*/drug effects ; Pyridines*/pharmacology; Animals ; Pyrimidinones/pharmacology ; Mice ; Pyridones/pharmacology ; Wound Healing/drug effects ; Dermis/transplantation ; Dermis/drug effects ; Graft Survival/drug effects ; Male ; Skin/drug effects ; Skin/blood supply ; Piperazines
    • Abstract:
      Full-thickness skin grafts often face challenges related to inefficient vascularization in clinical settings. Senescent cells, known for secreting various growth factors, have demonstrated excellent effects on angiogenesis. In this study, we induced senescence in a subset of fibroblasts in the donor dermis by co-administering trametinib and palbociclib before harvesting the skin grafts for transplantation. Grafts containing these senescent fibroblasts showed significant promotion of vascularization when surgically transplanted into recipient animals. This approach resulted in a 100% survival rate of the transplanted skin. Additionally, the senescent fibroblasts optimized wound healing and matrix remodeling, subsequently reducing inflammation and scar hyperplasia. Importantly, these senescent fibroblasts disappeared 14 days post-grafting, preventing excessive accumulation of senescent cells. Overall, our study indicates that inducing senescence in the donor dermis prior to transplantation is an effective strategy to enhance vascularization and increase the success rate of skin grafting.
      Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
      (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Full-thickness skin grafts; Revascularization; Senescence; Tissue engineering; Wound healing
    • Accession Number:
      0 (Pyridines)
      33E86K87QN (trametinib)
      0 (Pyrimidinones)
      0 (Pyridones)
      G9ZF61LE7G (palbociclib)
      0 (Piperazines)
    • Publication Date:
      Date Created: 20241218 Date Completed: 20241229 Latest Revision: 20241229
    • Publication Date:
      20241230
    • Accession Number:
      10.1016/j.ejphar.2024.177208
    • Accession Number:
      39694176