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

IF 4.2 3区 医学 Q1 PHARMACOLOGY & PHARMACY European journal of pharmacology Pub Date : 2025-01-15 DOI:10.1016/j.ejphar.2024.177208
Zhenjiang Li , Yulian Wang , Zhewei Yang , Jiayun Pang , Lin Song , Chunyan Liu , Junfeng Zhang , Lei Dong
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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.

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药物诱导的供体真皮成纤维细胞衰老促进皮肤移植的血运重建和移植成功。
在临床环境中,全层皮肤移植经常面临与低效率血管化相关的挑战。衰老细胞以分泌各种生长因子而闻名,在血管生成中表现出良好的作用。在这项研究中,我们在收获用于移植的皮肤移植物之前,通过联合施用曲美替尼和帕博西尼,诱导供体真皮中一部分成纤维细胞衰老。含有这些衰老成纤维细胞的移植物在手术移植到受体动物体内时显示出明显的血管化促进作用。这种方法使移植皮肤的存活率达到100%。此外,衰老的成纤维细胞优化伤口愈合和基质重塑,随后减少炎症和疤痕增生。重要的是,这些衰老的成纤维细胞在移植后14天消失,防止了衰老细胞的过度积累。总之,我们的研究表明,在移植前诱导供体真皮衰老是增强血管化和提高植皮成功率的有效策略。
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CiteScore
9.00
自引率
0.00%
发文量
572
审稿时长
34 days
期刊介绍: The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.
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