REVIEW article
Front. Cardiovasc. Med.
Sec. Atherosclerosis and Vascular Medicine
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1634877
Cross-Organ Protection of MSC-Derived Extracellular Vesicles in Ischemia-Reperfusion Injury: Angiogenic Synergy in Kidney, Brain, and Heart
Provisionally accepted
- Mianyang Central Hospital, Mianyang, China
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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 ischemiareperfusion 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 crossorgan protective responses. In this context, mesenchymal stem cell (MSC)-derived EVs have emerged as potent therapeutic agents for mitigating ischemia-reperfusion -2 -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 multiorgan ischemia-reperfusion injury management.
Keywords: Kidney, Brain, Heart, mesenchymal stem cell, extracellular vesicles, Angiogenic, ischemia-reperfusion injury
Received: 25 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Lai, Li, Luo, Qiu, Li and Dai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Min Dai, Mianyang Central Hospital, Mianyang, China
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