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

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...

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Bibliographic Details
Published in:European journal of pharmacology 2025-01, Vol.987, p.177208, Article 177208
Main Authors: Li, Zhenjiang, Wang, Yulian, Yang, Zhewei, Pang, Jiayun, Song, Lin, Liu, Chunyan, Zhang, Junfeng, Dong, Lei
Format: Article
Language:English
Subjects:
Animals
Cellular Senescence - drug effects
Dermis - drug effects
Dermis - transplantation
Fibroblasts - drug effects
Full-thickness skin grafts
Graft Survival - drug effects
Male
Mice
Neovascularization, Physiologic - drug effects
Piperazines
Pyridines - pharmacology
Pyridones - pharmacology
Pyrimidinones - pharmacology
Revascularization
Senescence
Skin - blood supply
Skin - drug effects
Skin Transplantation - methods
Tissue engineering
Wound healing
Wound Healing - drug effects
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Summary: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. [Display omitted]
ISSN:0014-2999
1879-0712
1879-0712
DOI:10.1016/j.ejphar.2024.177208