Si Jiaqian, Wang Jie, Dai Hao, Lv Tuochen, Zhao Songyun, Chen Wanying, Li Liqun, Ding Siqi, He Yucang
Department of Plastic Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Neurology, The Affiliated Yiwu hospital of Wenzhou Medical University, Yiwu, Zhejiang, China.
Front Cell Dev Biol. 2025 Jun 20;13:1621289. doi: 10.3389/fcell.2025.1621289. eCollection 2025.
Ischemia-reperfusion injury (IRI) has become a significant challenge for clinical treatment due to the complex multi-mechanism pathological cascade response, including oxidative stress, inflammatory bursts, and programmed cell death. Adipose-derived stem cells (ADSCs) and their exosomes (ADSCs-exosomes) are emerging as a breakthrough therapeutic strategy to reverse IRI, owing to their multi-target synergistic effects. This review systematically analyzes the two major repair modes of ADSCs and ADSCs-exosomes: the "common protection" mechanism, which includes anti-inflammatory, anti-oxidative, and anti-apoptotic effects through paracrine regulation of miRNAs targeting the NF-κB/NRF2/β-catenin signaling axis; and precision repair, which is achieved through organ-specific targets, including hepatic mitochondrial dynamics and pyroptosis inhibition, cardiac macrophage polarization and neutrophil clearance, renal anti-fibrosis and erythropoietin (EPO) activation, as well as brain iron death regulation and microglial remodeling. From the perspective of the mechanism interaction network, this paper first proposes a theoretical framework of "multi-organ shared core pathways and dynamic regulation of different targets." It also reviews the translational potential of combined therapeutic strategies based on engineered exosomes delivery systems and biomaterials, emphasizing the optimization of delivery efficiency and functional enhancement to address the bottleneck of clinical applications. The ADSCs-mediated IRI intervention system provides an essential theoretical and technical basis for the development of individualized precision therapies.
由于包括氧化应激、炎症爆发和程序性细胞死亡在内的复杂多机制病理级联反应,缺血再灌注损伤(IRI)已成为临床治疗的一项重大挑战。脂肪干细胞(ADSCs)及其外泌体(ADSCs-外泌体)因其多靶点协同作用,正成为逆转IRI的突破性治疗策略。本综述系统分析了ADSCs和ADSCs-外泌体的两种主要修复模式:“共同保护”机制,包括通过对靶向NF-κB/NRF2/β-连环蛋白信号轴的miRNAs进行旁分泌调节来发挥抗炎、抗氧化和抗凋亡作用;以及精准修复,这是通过器官特异性靶点实现的,包括肝脏线粒体动力学和焦亡抑制、心脏巨噬细胞极化和中性粒细胞清除、肾脏抗纤维化和促红细胞生成素(EPO)激活,以及脑铁死亡调节和小胶质细胞重塑。本文从机制相互作用网络的角度,首次提出了“多器官共享核心通路及不同靶点动态调节”的理论框架。本文还综述了基于工程化外泌体递送系统和生物材料的联合治疗策略的转化潜力,强调优化递送效率和功能增强以解决临床应用瓶颈。ADSCs介导的IRI干预系统为个性化精准治疗的发展提供了重要的理论和技术基础。