Lai Zhuhong, Li Dong, Luo Caidong, Qiu Qingyan, Li Rong, Dai Min
Department of Cardiology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
Front Cardiovasc Med. 2025 Aug 19;12:1634877. doi: 10.3389/fcvm.2025.1634877. eCollection 2025.
Ischemia-reperfusion injury, marked by transient blood flow disruption followed by tissue reperfusion, constitutes a unifying pathological mechanism across cerebral stroke, myocardial infarction, and acute kidney injury. Hypoxia, a central driver of ischemia-reperfusion injury progression, triggers molecular cascades that simultaneously exacerbate tissue damage and activate compensatory repair mechanisms. Notably, hypoxia-induced angiogenesis and vascular remodeling serve as critical adaptive processes for functional recovery, supporting neuronal plasticity in stroke, myocardial salvage in infarction, and tubular regeneration in renal ischemia-reperfusion injury. While these conditions exhibit organ-specific manifestations, emerging studies underscore conserved regulatory frameworks mediated by extracellular vesicles (EVs) and their molecular cargoes, which orchestrate cross-organ protective responses. In this context, mesenchymal stem cell (MSC)-derived EVs have emerged as potent therapeutic agents for mitigating ischemia-reperfusion injury-related deficits, as evidenced by preclinical and clinical studies. These EVs act as bioactive nanocarriers, delivering cargos that modulate shared pathological pathways-particularly angiogenesis, a linchpin of post-ischemic tissue repair. Accumulating evidence highlights cargos within MSC-EVs (e.g., miRNAs, proteins) as master regulators of vascular regeneration, fine-tuning endothelial proliferation, vessel maturation, and hypoxia adaptation. This review systematically examines the dual roles of MSC-EV-associated cargos in promoting or suppressing angiogenesis across cerebral, cardiac, and renal ischemia-reperfusion injury models. By dissecting their mechanisms in spatiotemporal regulation of vascular signaling networks, we aim to elucidate their translational potential as universal therapeutic targets for multi-organ ischemia-reperfusion injury management.
缺血再灌注损伤以短暂的血流中断随后组织再灌注为特征，是贯穿脑卒 中、心肌梗死和急性肾损伤的统一病理机制。缺氧是缺血再灌注损伤进展的核心驱动因素，触发分子级联反应，同时加剧组织损伤并激活代偿性修复机制。值得注意的是，缺氧诱导的血管生成和血管重塑是功能恢复的关键适应性过程，支持卒中后的神经元可塑性、梗死心肌的挽救以及肾缺血再灌注损伤中的肾小管再生。虽然这些病症表现出器官特异性表现，但新兴研究强调了由细胞外囊泡（EV）及其分子货物介导的保守调节框架，这些框架协调跨器官的保护反应。在这种情况下，间充质干细胞（MSC）衍生的EV已成为减轻缺血再灌注损伤相关缺陷的有效治疗剂，临床前和临床研究均证明了这一点。这些EV作为生物活性纳米载体，递送调节共同病理途径的货物，特别是血管生成，这是缺血后组织修复的关键。越来越多的证据表明，MSC-EV中的货物（如miRNA、蛋白质）是血管再生的主要调节因子，可微调内皮细胞增殖、血管成熟和缺氧适应。本综述系统地研究了MSC-EV相关货物在促进或抑制脑、心脏和肾缺血再灌注损伤模型中的血管生成方面的双重作用。通过剖析它们在血管信号网络时空调节中的机制，我们旨在阐明它们作为多器官缺血再灌注损伤管理的通用治疗靶点的转化潜力。
