From Brain to Lung: Emerging Insights into Mesenchymal Stem Cell-Derived Extracellular Vesicle-Associated Cargos in Ischemia-Reperfusion Injury.

Ischemic stroke represent major global health challenges due to their high incidence and debilitating consequences. Similarly, lung ischemia-reperfusion injury has gained increasing attention in the medical research community. The emerging concept of the lung-brain axis has shed new light on the complex interplay between these two organ systems during pathological injury, demonstrating that their interaction can significantly exacerbate ischemia- reperfusion damage. Although these conditions exhibit distinct pathophysiological characteristics, they share remarkable similarities in their genetic responses to tissue injury. Recent advancements in regenerative medicine have highlighted the therapeutic potential of mesenchymal stem cells (MSCs) in addressing both ischemic stroke and lung ischemia-reperfusion injury. Particularly, extracellular vesicles (EVs) derived from MSCs have emerged as a promising therapeutic avenue. These MSC-derived EVs exert their protective effects through multiple mechanisms, including immunomodulation, anti-inflammatory actions, anti-apoptotic effects, oxidative stress regulation, and promotion of angiogenesis. This comprehensive review aims to systematically examine the therapeutic roles of MSC-derived EVs in both cerebral and pulmonary ischemia-reperfusion injuries, while emphasizing their shared pathological mechanisms. By elucidating these common pathways, we hope to provide novel perspectives and research directions for both clinical and basic investigations into lung-brain ischemia-reperfusion injury.