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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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Published in: | European journal of pharmacology 2025-01, Vol.987, p.177208, Article 177208 |
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container_title | European journal of pharmacology |
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creator | Li, Zhenjiang Wang, Yulian Yang, Zhewei Pang, Jiayun Song, Lin Liu, Chunyan Zhang, Junfeng Dong, Lei |
description | 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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doi_str_mv | 10.1016/j.ejphar.2024.177208 |
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[Display omitted]</description><identifier>ISSN: 0014-2999</identifier><identifier>ISSN: 1879-0712</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2024.177208</identifier><identifier>PMID: 39694176</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>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</subject><ispartof>European journal of pharmacology, 2025-01, Vol.987, p.177208, Article 177208</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1566-5217f7d63dcdc6844acb288eea2e9a3f9f37833c7a00da2672f0d4811d76d123</cites><orcidid>0000-0002-2013-4191 ; 0009-0003-7680-9391 ; 0009-0003-9429-1311 ; 0000-0001-9025-8838 ; 0009-0005-3927-2067 ; 0009-0002-6087-2559</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39694176$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zhenjiang</creatorcontrib><creatorcontrib>Wang, Yulian</creatorcontrib><creatorcontrib>Yang, Zhewei</creatorcontrib><creatorcontrib>Pang, Jiayun</creatorcontrib><creatorcontrib>Song, Lin</creatorcontrib><creatorcontrib>Liu, Chunyan</creatorcontrib><creatorcontrib>Zhang, Junfeng</creatorcontrib><creatorcontrib>Dong, Lei</creatorcontrib><title>Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>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]</description><subject>Animals</subject><subject>Cellular Senescence - drug effects</subject><subject>Dermis - drug effects</subject><subject>Dermis - transplantation</subject><subject>Fibroblasts - drug effects</subject><subject>Full-thickness skin grafts</subject><subject>Graft Survival - drug effects</subject><subject>Male</subject><subject>Mice</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Piperazines</subject><subject>Pyridines - pharmacology</subject><subject>Pyridones - pharmacology</subject><subject>Pyrimidinones - pharmacology</subject><subject>Revascularization</subject><subject>Senescence</subject><subject>Skin - blood supply</subject><subject>Skin - drug effects</subject><subject>Skin Transplantation - methods</subject><subject>Tissue engineering</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>0014-2999</issn><issn>1879-0712</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNp9kMtuFDEQRS0EIkPgDxDykk0PfvTY7Q0SCk8pEpvsrRq7nHjocQ-u7gj4ejx0YMmmanNuPQ5jL6XYSiHNm8MWD6c7qFslVL-V1ioxPGIbOVjXCSvVY7YRQvadcs5dsGdEByHEzqndU3ahnXG9tGbDfryvy22XS1wCRk5YkAKWgHxKPE5lqjxiPcLIU97XaT8CzcSx3EFjiFe8BwrLCDX_gjlPhUOJ_LZCmjktoSHEc-H0rZW5QqHTCGX-Qz5nTxKMhC8e-iW7-fjh5upzd_3105erd9ddkDtjup2SNtlodAwxmKHvIezVMCCCQgc6uaTtoHWwIEQEZaxKIvaDlNGaKJW-ZK_Xsac6fV-QZn_M7cOx3YHTQl7L3krdRA0N7Vc01ImoYvKnmo9Qf3op_Fm5P_hVuT8r96vyFnv1sGHZHzH-C_113IC3K4DtzfuM1VPIZ8cxVwyzj1P-_4bfKgmWww</recordid><startdate>20250115</startdate><enddate>20250115</enddate><creator>Li, Zhenjiang</creator><creator>Wang, Yulian</creator><creator>Yang, Zhewei</creator><creator>Pang, Jiayun</creator><creator>Song, Lin</creator><creator>Liu, Chunyan</creator><creator>Zhang, Junfeng</creator><creator>Dong, Lei</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2013-4191</orcidid><orcidid>https://orcid.org/0009-0003-7680-9391</orcidid><orcidid>https://orcid.org/0009-0003-9429-1311</orcidid><orcidid>https://orcid.org/0000-0001-9025-8838</orcidid><orcidid>https://orcid.org/0009-0005-3927-2067</orcidid><orcidid>https://orcid.org/0009-0002-6087-2559</orcidid></search><sort><creationdate>20250115</creationdate><title>Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation</title><author>Li, Zhenjiang ; Wang, Yulian ; Yang, Zhewei ; Pang, Jiayun ; Song, Lin ; Liu, Chunyan ; Zhang, Junfeng ; Dong, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1566-5217f7d63dcdc6844acb288eea2e9a3f9f37833c7a00da2672f0d4811d76d123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Animals</topic><topic>Cellular Senescence - drug effects</topic><topic>Dermis - drug effects</topic><topic>Dermis - transplantation</topic><topic>Fibroblasts - drug effects</topic><topic>Full-thickness skin grafts</topic><topic>Graft Survival - drug effects</topic><topic>Male</topic><topic>Mice</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Piperazines</topic><topic>Pyridines - pharmacology</topic><topic>Pyridones - pharmacology</topic><topic>Pyrimidinones - pharmacology</topic><topic>Revascularization</topic><topic>Senescence</topic><topic>Skin - blood supply</topic><topic>Skin - drug effects</topic><topic>Skin Transplantation - methods</topic><topic>Tissue engineering</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zhenjiang</creatorcontrib><creatorcontrib>Wang, Yulian</creatorcontrib><creatorcontrib>Yang, Zhewei</creatorcontrib><creatorcontrib>Pang, Jiayun</creatorcontrib><creatorcontrib>Song, Lin</creatorcontrib><creatorcontrib>Liu, Chunyan</creatorcontrib><creatorcontrib>Zhang, Junfeng</creatorcontrib><creatorcontrib>Dong, Lei</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zhenjiang</au><au>Wang, Yulian</au><au>Yang, Zhewei</au><au>Pang, Jiayun</au><au>Song, Lin</au><au>Liu, Chunyan</au><au>Zhang, Junfeng</au><au>Dong, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2025-01-15</date><risdate>2025</risdate><volume>987</volume><spage>177208</spage><pages>177208-</pages><artnum>177208</artnum><issn>0014-2999</issn><issn>1879-0712</issn><eissn>1879-0712</eissn><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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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 |
title | Drug-induced senescence of donor dermal fibroblasts enhances revascularization and graft success in skin transplantation |
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