Lai Hongbin, Lin Ling, Pan Yanrui, Wang Boqun, Ma Lan, Zhao Wei
Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.
South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.
Pharmaceutics. 2025 Apr 1;17(4):453. doi: 10.3390/pharmaceutics17040453.
This study aimed to explore the therapeutic potential of umbilical mesenchymal stem cell-derived apoptotic vesicles (UMSC-apoVs) in a 5-Fluorouracil (5-FU)-induced impairment in skin wound healing. UMSC-apoVs were isolated from UMSCs using differential centrifugation after the induction of apoptosis. A murine model was established by administering 5-FU via intravenous tail injection, followed by full-thickness skin wound creation. Mice received local injections of UMSC-apoVs at the lesion site. Wound healing was evaluated based on wound closure rates, histological analysis, and in vivo/in vitro functional assays. Rotenone (Rot)-pretreated UMSC-apoVs were used to explore the role of mitochondrial transfer between skin mesenchymal stem cells (SMSCs) and UMSC-apoVs in wound healing. UMSC-apoVs significantly accelerated wound healing in 5-FU-treated mice, as demonstrated by enhanced wound closure rates and histological findings of reduced inflammatory infiltration and increased collagen deposition. UMSC-apoVs transferred mitochondria to SMSCs, enhancing viability, proliferation, and migration while reducing reactive oxygen species (ROS) production in SMSCs. Rot pretreatment inhibited the therapeutic effects of UMSC-apoVs on wound healing by inducing mitochondrial dysfunction in UMSC-apoVs. Our findings indicate that UMSC-apoVs improve 5-FU-induced impaired skin wound healing by facilitating mitochondrial transfer, suggesting a novel therapeutic strategy for alleviating chemotherapy-induced impairment in wound healing.
本研究旨在探讨脐间充质干细胞来源的凋亡小泡（UMSC-apoVs）在5-氟尿嘧啶（5-FU）诱导的皮肤伤口愈合受损中的治疗潜力。在诱导凋亡后，通过差速离心从脐间充质干细胞中分离出UMSC-apoVs。通过尾静脉注射5-FU建立小鼠模型，随后进行全层皮肤伤口造模。小鼠在损伤部位接受UMSC-apoVs局部注射。基于伤口闭合率、组织学分析以及体内/体外功能测定来评估伤口愈合情况。使用鱼藤酮（Rot）预处理的UMSC-apoVs来探究皮肤间充质干细胞（SMSC）与UMSC-apoVs之间的线粒体转移在伤口愈合中的作用。UMSC-apoVs显著加速了5-FU处理小鼠的伤口愈合，表现为伤口闭合率提高以及炎症浸润减少和胶原沉积增加的组织学结果。UMSC-apoVs将线粒体转移至SMSC，增强了其活力、增殖和迁移能力，同时减少了SMSC中的活性氧（ROS）生成。Rot预处理通过诱导UMSC-apoVs中的线粒体功能障碍抑制了UMSC-apoVs对伤口愈合的治疗作用。我们的研究结果表明，UMSC-apoVs通过促进线粒体转移改善了5-FU诱导的皮肤伤口愈合受损，提示了一种减轻化疗诱导的伤口愈合受损的新治疗策略。
